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Department of Molecular and Integrative Physiology, University of Illinois (J.F., J.M.D., B.S.K.), Urbana, Illinois 61801; and Women’s Health Research Institute, Wyeth Research (B.K., K.C.N.C., C.R.L.), Collegeville, Pennsylvania 19426
Address all correspondence and requests for reprints to: Dr. Benita S. Katzenellenbogen, Department of Molecular and Integrative Physiology, University of Illinois, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801-3704. E-mail: katzenel{at}life.uiuc.edu.
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Abstract |
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Introduction |
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The ER uses multiple mechanisms to either activate or repress transcription of its target genes. These mechanisms include 1) direct interaction of the ligand-occupied receptor with DNA at estrogen response elements, followed by recruitment of transcriptional coregulator or mediator complexes; 2) interaction of the ligand-occupied ER with other transcription factors, such as activating protein-1 (AP-1) (4), Sp1 (5), or nuclear factor-
B (NF-B) (6); or 3) indirect modulation of gene transcription via sequestration of general/common transcriptional components (7, 8). To add a further layer of complexity, the ability of ER to regulate transcription through these various mechanisms appears to be cell type specific, perhaps due to differences in the complement of transcriptional coregulatory factors available in each cell type (9, 10, 11). Also, transcriptional regulation is dependent upon the nature of the ligand, with various natural and synthetic selective ER modulators (SERMs) acting as either ER agonists or antagonists through each of these various mechanisms (12, 13, 14, 15).
With the sequencing of the human genome as well as the advent of microarray technology, it is now possible to investigate the complexities of ER-mediated gene transcription on a more global scale rather than one estrogen-responsive target gene at a time. One area where this would be of great importance is in the study of the regulation of gene expression by both estrogens and SERMs, such as tamoxifen or raloxifene, in ER-positive breast cancer. The effects of estradiol (E2) on increased breast cancer cell proliferation and tumorigenesis have been well documented, and several recent studies using microarray techniques have begun to document the gene expression profiles in breast cancer. Most of these studies have focused on identifying genes overexpressed in breast cancer (16) or patterns of gene expression associated with clinical outcome or prognosis (17, 18), responses to chemotherapy or drug resistance (19), tumor aggressiveness (20), or classification of primary tumors (21, 22, 23). The role of ER expression has also been addressed in several studies in which distinct gene expression patterns associated with ER status have been identified (24, 25, 26).
Despite these recent investigations, the exact role of estrogen-mediated gene regulation in ER-positive breast cancer and the manner in which these changes in gene expression affect breast cancer proliferation and progression are far from clear. Relatively few microarray studies have examined the role of estrogens in regulating gene expression, and the studies that have been performed in breast cancer cells have been on a relatively limited scale, with few genes examined or over a limited time course of hormone treatment (27, 28, 29, 30).
In this study the ER-positive breast cancer cell line MCF-7 was treated with E2 for different times up to 48 h, and gene expression profiling was carried out using the Affymetrix human GeneChip U95A, which contains oligonucleotide probes for approximately 12,000 human genes. Our findings reveal that E2 regulates gene expression with several distinct time-course patterns, that almost 70% of the genes regulated by E2 are, in fact, down-regulated, and that numerous cell cycle-associated genes as well as expression of novel transcription factors, receptors, and signaling pathways are modulated by E2, many of which could play roles in mediating the effects of E2 on breast cancer proliferation and cell phenotype.
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Materials and Methods |
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GeneChip microarrays
Total RNA was used to generate cRNA, which was labeled with biotin according to techniques recommended by Affymetrix (Santa Clara, CA). cRNA was then hybridizd to Affymetrix Hu95A GeneChips, which contain approximately 12,000 human oligonucleotide probe sets. After washing, the chips were scanned and analyzed using MicroArray Suite 5.0 (Affymetrix). Average intensities for each GeneChip were globally scaled to a target intensity of 150. Further analysis was performed using GeneSpring software version 5.0.1 (Silicon Genetics, Redwood City, CA) to obtain fold change and P values for each gene at each time point relative to untreated control.
Identification of E2-regulated genes
To identify genes significantly regulated by E2 treatment, a confidence score (CS) was calculated for each gene at each time point of E2 treatment, based on the report by Jelinksy et al. (31) with some modifications. The CS was defined as the sum of individual scores given for fold change (FC), P value (PV), expression level (EL), and present calls (PC), so that CS = FC + PV + EL + PC. The score for FC was 5 if the fold change was 2.0 or more for stimulated genes or 0.5 or less for inhibited genes, it was 2 if the fold change was more than 1.5 for stimulated genes or less than 0.67 for inhibited genes, and it was -0.5 if the fold change was less than 1.5 or 0.67 or more for stimulated or inhibited genes, respectively. The PV score was 3 if P < 0.05, it was 2 if P < 0.1, and it was -0.5 if P 
0.1. The expression level was based on the scaled intensity for each gene, with the EL score being 3 if the intensity was more than 20, 1 if the intensity was more than 15, or -0.5 if the intensity was 15 or less. The PC score was 3 if the gene was present in at least two of the four samples, was 1 if the gene was present in only one of the four samples, or was -0.5 if the gene was absent. Based on this scoring, the maximum CS for any gene would be 14.0. We considered a gene to be significantly regulated by E2 if the CS was 12.0 or greater. Our selection of this CS identified genes known to be estrogen regulated and gave highly reproducible patterns of regulation for newly identified genes.
Real-time PCR
Real-time PCR was carried out on over 50 genes to verify the regulation of expression by E2. One microgram of total RNA was reverse transcribed in a total volume of 20 µl using 200 U reverse transcriptase, 50 pmol random hexamer, and 1 mM deoxy-NTP (New England Biolabs, Beverly, MA). The resulting cDNA was then diluted to a total volume of 100 µl with sterile H2O. Each real-time PCR reaction consisted of 1 µl diluted RT product, 1x SYBR Green PCR Master Mix (PE Applied Biosystems, Foster City, CA), and 50 nM forward and reverse primers. Reactions were carried out on an ABI PRISM 7700 Sequence Detection System (PE Applied Biosystems) for 40 cycles (95 C for 15 sec, 60 C for 1 min) after an initial 10-min incubation at 95 C. For the genes whose regulation is described in detail in this report, the primers used for real-time PCR are listed in Table 1
. The fold change in expression of each gene was calculated using the 
Ct method, with the ribosomal protein 36B4 mRNA as an internal control (32).
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Results |
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Time-course patterns of gene regulation
Three types of analyses were performed to identify different patterns of gene regulation based on the time course of E2 treatment. First, gene cluster analysis was performed using GeneSpring software (Fig. 1A). Each row represents a single time point (0–48 h) and contains all 438 regulated genes, with stimulated genes in red, inhibited genes in blue, and genes not different from control in yellow. The pattern for each cluster of genes can be observed vertically over the different treatment times. Using this method, several patterns of E2 regulation are visible, as is the fact that the majority of genes are inhibited by E2. Clusters labeled A through C demonstrate three patterns of stimulated genes, with A showing genes highly regulated at all time points examined, B showing genes stimulated at the earlier time points only, and C showing genes stimulated only at the later time points. Clusters labeled D and E show two patterns of down-regulated genes: genes highly down-regulated at all time points (in D) and genes down-regulated at later time points only (in E).
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). In these plots, the normalized signal for each of the E2-regulated genes at the time of interest is plotted on the y-axis against the control signal on the x-axis. The outer diagonal lines represent 2-fold changes in expression. This type of analysis demonstrates that at early time points, a greater proportion of genes are up-regulated by E2 (red) compared with down-regulated genes (blue), whereas at later time points a far greater number of genes are down-regulated in relation both to early time points and to the number of up-regulated genes.
These observations were confirmed using a third analysis (Fig. 2), in which the 438 genes regulated by E2 were assigned to one of three distinct patterns: 1) regulated early only (2-fold at 4 and/or 8 h only), 2) regulated early and late (2-fold at 4 and/or 8 h and at 24 and/or 48 h), or 3) regulated late only (2-fold at 24 and/or 48 h only). For stimulated genes, an approximately equal number of genes were observed in each of the 3 patterns (early, n = 44; early and late, n = 46; late, n = 42), with the most robustly stimulated genes in the early and late patterns (Fig. 2, left panel). In contrast, very few inhibited genes showed the early only pattern (n = 11), with the majority of genes being down-regulated at either the early and late (n = 110) or the late time points only (n = 185; Fig. 2, right panel). As our first time point was 4 h, it is possible that some additional early response genes may not have been identified.
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) include apoptosis, cell adhesion/extracellular matrix, cell cycle, cytoskeleton/structural, enzymes/metabolism, growth factors/hormones/cytokines, nucleotide processing, protein processing, receptors, signal transduction, transcription, and transporters. With a few exceptions, the proportion of stimulated to inhibited genes in each category was similar (Fig. 3). A substantially greater proportion of genes involved in cell cycle and nucleotide processing, such as DNA repair or RNA splicing, were stimulated by E2, whereas a greater proportion of cell adhesion and extracellular matrix genes as well as enzymes were inhibited by E2.
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). The time courses of regulation for the known E2-stimulated genes cyclin D1 and cell division cycles 2 and 20 (CDC2 and CDC20) are shown in Fig. 4A. Figure 4B shows real-time PCR data for the time course of identified E2-stimulated genes, minichromosome maintenance genes (MCM2, MCM3, and MCM5), CDC6, and replication factor C4 (RFC4), all of which have roles in DNA synthesis. Of interest, the time course information indicates that the majority of cell cycle-associated genes that are stimulated by E2 are regulated late, at 24 h or later. Only cyclin D1 and CDC6 are up-regulated by E2 within the first 4 h of treatment.
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and Fig. 4C). Two members of the pheochromacytoma cell-3 (PC3)/B cell translocation gene (BTG)/transducer of ERBB2 (TOB) family, BTG-1 and BTG-2, which have been shown to be induced by p53 and to inhibit cell cycle progression, are down-regulated by E2, although their precise molecular functions are not known (33). Also down-regulated by E2 is cyclin G2, a gene known to induce cell cycle arrest and to be up-regulated when cells undergo arrest or apoptosis (34). It also appears that E2 may influence not only proliferation, but also cell survival through the up-regulation of the antiapoptotic gene survivin and the down-regulation of multiple proapoptotic genes, including BCL 2-interacting killer, BCL-2 antagonist/killer 1, immediate early response 3 (also known as IEX-1), and caspase 9. Hence, E2 acts to stimulate genes associated with cell proliferation, in particular genes associated with DNA synthesis, as well as to down-regulate antiproliferative and proapoptotic genes, probably leading to an overall increase in both proliferation and cell survival.
E2 regulation of genes encoding growth factors, cytokines and hormones
Our findings support the proposal (35) that major changes in breast cancer cell proliferation by E2 involve the up-regulation of growth factors that can act in an autocrine manner. We have found several growth factors, cytokines, and hormones to be regulated by E2 in MCF-7 cells (Table 3). Amphiregulin, stromal cell-derived factor 1 (SDF-1; also known as chemokine ligand 12), stanniocalcin 2, and vascular endothelial growth factor (VEGF), all previously identified as E2-stimulated genes, showed early increases after E2 exposure, and as shown in Fig. 5, each of these genes had a unique time course of regulation, with amphiregulin and SDF-1 showing sustained high fold stimulated levels over the 48 h, and VEGF and stanniocalcin being elevated primarily at early times only.
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and Fig. 5). These data highlight that in addition to the stimulation of growth factors associated with increased cell proliferation, down-regulation of several growth inhibitory factors, particularly members of the TGFß family, including TGFß3, BMP4, and inhibin ßB, may contribute to the increased proliferation elicited by E2.
E2 regulation of receptors and signaling pathways
A significant number of receptors and signaling molecules were found to be regulated by E2, particularly at early times (Table 4). Two pathways of note, which are regulated at several levels, include the prostaglandin E pathway (Fig. 6A) and SDF-1 (up-regulated by E2; as shown in Fig. 5) and its chemokine receptor CXCR4 (Fig. 6B) pathway. The enzyme prostaglandin E synthase as well as the prostaglandin E receptor (EP3) were found to be stimulated by E2 (Fig. 6A). In contrast, the CXCR4 receptor, which may play a role in cell motility, was down-regulated by E2, as was BLNK (Fig. 6B), a B cell scaffolding protein that is involved in regulating the activity of CXCR4 (36). These findings suggest an overall decrease in signaling through the CXCR4 pathway, but an increase in prostaglandin E production and signaling in response to E2.
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) and the down-regulated erythropoietin receptor, IL-1 receptor type I, and Notch 3, which are rapidly decreased, by 4 and 8 h (Fig. 6D).
E2 regulation of transcription factors and transcriptional coregulators
Many novel transcription factors, including HOXC4, HOXC5, and HOXC6, were identified as being markedly stimulated by E2 (Fig. 7A and Table 5). Interestingly, these three genes had an identical time course of E2 regulation, with the maximum stimulation at 4 h, followed by a decrease. However, it should be noted that HOXC4 showed a much higher degree of stimulation and remained greatly elevated throughout the entire 48-h time course. The biological significance of these differences is not clear.
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). However, our time-course analysis reveals some new information about E2 regulation of several of these factors. One example is that of the oncogene c-myb and two related transcription factors, A-Myb and B-Myb (also known as myb-like 1 and myb-like 2). All three were stimulated by E2, but had very different time courses and magnitudes of regulation (Fig. 7B). Both A-Myb and C-Myb were highly up-regulated within 4 h of E2 treatment and remained elevated throughout the 48 h, with the level of A-Myb stimulation being approximately three to four times greater at all time points. In contrast, B-Myb was not significantly up-regulated by E2 until 24 h of treatment, at which time a 4- to 5-fold stimulation was observed. This suggests that although these three related transcription factors are stimulated by E2, their regulation may be through different mechanisms. Indeed, studies with the protein synthesis inhibitor, cycloheximide (Fig. 7C), reveal that the rapidly up-regulated A-Myb and C-Myb genes are probably primary response genes as their stimulation is not blocked by cycloheximide whereas B-Myb, the more slowly responding gene is probably a secondary response gene, as its stimulation is prevented by cycloheximide treatment. Indeed, it is likely that the early changes in the expression of genes encoding transcription factors could impact the expression of later downstream genes.
Also of interest, a number of transcription factors thought to be transcriptional repressors were down-regulated by E2 (Fig. 8). These include Mad4, JunB, an Ets2 repressor factor (ERF), and two members of the Id family of transcriptional regulators, inhibitor of DNA binding 1 and 2. We also found mRNA encoding the high-mobility group (HMG) box-containing protein 1 (HBP1) and SATB1, an AT-rich binding protein and nuclear matrix scaffolding factor, to be down-regulated by E2, and the down-regulations observed by Affymetrix microarray analysis were confirmed by real-time PCR (Fig. 8B). The suppression of gene expression for multiple transcriptional repressors might enable E2 to increase the transcriptional activity of genes in numerous pathways in breast cancer cells.
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, there appears to be a change in the complement of cell coregulators, with a down-regulation of steroid receptor coactivator (SRC)-2/glucocorticoid receptor interacting protein 1/transcriptional intermediary factor (TIF)2, SRC-3/amplified in breast cancer 1/ACTR (a novel coactivator), and TIF1
(37), as well as two other enhancers of ER activity, a small proline-rich coactivator termed PNRC2 (38) and SMAD3 [Sma and mothers against decapentaplegic (MAD) homolog 3], another transcription factor known to enhance ER activity (39). In contrast, the only coregulator we observed to be stimulated by E2 was receptor-interacting protein 140/nuclear receptor-interacting protein 1 (Table 5); it generally functions as a corepressor of ER, but can also exhibit coactivator activity and has previously been reported to be regulated by E2 (40).
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Many genes affected by E2 are down-regulated
Of the more than 12,000 genes queried on the Affymetrix U95A microarray, we identified over 400 genes that showed a robust pattern of regulation by E2, but notably the majority of these genes (70%) were, in fact, down-regulated. Although there may be multiple mechanisms involved in this down-regulation, two mechanisms by which E2 has been shown to repress gene expression involve the inhibition of NF-B, such as occurs for E2 down-regulation of IL-6, or squelching/sequestering of shared transcriptional coactivators that might be necessary for maintaining basal gene expression (6, 7, 8). Both mechanisms seem plausible, as NF-B signaling has been detected in breast cancer cells and has been implicated in the progression of breast cancer from ER-positive to ER-negative status (41, 42). Also, our finding that multiple transcriptional coactivators are down-regulated by E2 suggests that some of the estrogen-induced down-regulation of genes could be due at least in part to changes in levels of limiting transcriptional coregulators.
Time course and level of regulation: primary vs. secondary responses
The time-course studies we have performed, spanning times up to 48 h, reveal a diversity of temporal patterns of gene regulation by E2. One can use these patterns as a general guide to assist in identifying genes that are likely to be primary responses vs. secondary responses to the hormone. Although genes that show rapid changes in mRNA levels are likely to be primary response genes, and those that show a lag before changing are likely to be secondary, the half-life of the specific mRNA will also be an important factor in determining how long it takes to detect a change, either up or down, in the mRNA level of a specific gene.
A more definitive way to distinguish primary from secondary responses often employs the use of cycloheximide, which should not affect primary gene responses, but should block secondary mRNA responses. We chose to probe this point in one particular case, that of the three Mybs. As seen in Fig. 7C, the A-, B-, and C-Myb transcription factors were all stimulated by E2, with the changes in A- and C-Myb being rapid, but B-Myb showing a distinct lag before stimulation. Cycloheximide had no effect on A- and C-Myb stimulation, but blocked B-Myb stimulation very effectively, indicating that the two genes that showed the rapid response were primary, whereas the gene with the late pattern of increase was not a primary response gene. Thus, in this case the time course of response to estrogen was predictive of primary vs. secondary gene responsiveness. Although time-course data can be useful as a general guide, definitive determination of whether a gene response is primary would need to be evaluated in genes of interest individually.
Motifs in the regulation of proliferation: up-regulation of positive and down-regulation of negative factors
E2 up-regulates genes such as cyclin D1, cyclin A2, cdc2 (cdk1), cdc20, and some novel genes we identified, such as Bub1, that are involved in the progression of the cell cycle, and genes involved in DNA synthesis, such as RFC4, proliferating cell nuclear antigen, CDC6, and MCM proteins 2, 3, and 5. Interestingly, the gene survivin (BIRC5), which encodes an inhibitor of apoptosis, was found by us to be up-regulated by E2 and has recently been shown to protect MCF-7 cells from etoposide-induced apoptosis (43). Other positive growth-promoting effects of E2 occur through the induction of growth factors and transcription factors, such as SDF-1, which was recently shown to play a role in E2 induced ovarian cancer cell proliferation (44). Interestingly, the transcription factors HOXC6 and A-Myb, which we found to be highly induced by E2 at early time points, have both been shown through mouse knockout models to be required for normal mammary gland development (45, 46). Although HOXC6 is essential for normal mammary gland development, it noteworthy that its synthesis is actually down-regulated by E2 in normal mouse mammary gland epithelium (45). Whether the up-regulation of HOXC6 or the primary induction of A-Myb by E2 in breast cancer cells contributes to the progression of breast cancer cell proliferation is currently under investigation.
Perhaps the most novel finding of this work is that E2-induced enhancement of cell proliferation and of cell cycle progression is associated with the down-regulation of numerous factors that are known to inhibit the cell cycle. Hence, E2 down-regulates genes directly involved in inhibition of the cell cycle, such as BTG-1, BTG-2, and cyclin G2, and also down-regulates cytokines and growth factors that are known to inhibit cell proliferation, such as members of the TGFß superfamily. Although TGF-ß3 is known to be down-regulated by E2 in MCF-7 cells and to inhibit breast cancer cell proliferation (47), BMP4 has not yet been shown to play a role in breast cancer. It is known to be stimulated by antiestrogens in bone cells, but it has not previously been implicated in playing a role in breast cancer, whereas BMP2 is known to inhibit breast cancer cell proliferation, suggesting that, like BMP2 and TGFß, BMP4 may also be growth inhibitory (48, 49). In addition, activin is growth inhibitory to breast cancer cells (41, 45), and it is of interest that its subunit inhibin ßB was significantly down-regulated by E2.
E2 down-regulation of multiple transcriptional repressors could also contribute to increased cell proliferation. For example, Mad4 antagonizes Myc action by competing for their binding partner Max and forming dimers with Max that bind to E boxes in Myc target genes, thereby repressing transcription (50). Thus, E2 could enhance Myc activity not only by up-regulating c-Myc, but additionally by down-regulating an inhibitor of Myc. Also, the transcription factor JunB, which is a member of the AP-1 transcription factor family, may act as a negative regulator of transcription through AP-1, particularly in the presence of c-Jun and when acting on cell proliferation-associated genes (51). Therefore, by up-regulation of c-Fos and down-regulation of JunB, E2 could further enhance growth stimulatory gene transcription through AP-1. Other transcriptional repressors whose down-regulation by E2 may contribute to enhanced cell proliferation include HBP1, which can represses Wnt signaling (52, 53), and ERF, which represses the transcription of promoters containing an ets-binding site and is inactivated by the Ras/MAPK pathway (54). This down-regulation of multiple transcriptional repressors (such as JunB, Mad4, HBP1, and ERF) suggests that one major function of E2 in breast cancer cells is perhaps to increase the transcriptional activity of numerous cell transduction pathways, several of which appear to be involved in the regulation of cell proliferation.
E2 modification of its own synthesis and of ER actions
A particularly interesting regulatory loop that may contribute to the amplification of E2-induced processes is that involving prostaglandin and prostaglandin receptors, and the genes that they regulate. Prostaglandin E synthase (also known as PIG12) (55) and prostaglandin E receptor type 3 (EP3) were found to be up-regulated by E2. By up-regulating prostaglandin E synthase, estrogen could be increasing the production of prostaglandin E2. This hormone can act on the prostaglandin EP1 or EP2 receptors to stimulate aromatase activity in breast cancer, thereby raising estrogen levels in these cells (56). This suggests the intriguing possibility that E2 could be up-regulating its own synthesis in a feedforward cascade that involves up-regulation of prostaglandin E synthase and the subsequent action of increased prostaglandin E2 levels on prostaglandin receptors, which would up-regulate the aromatase gene.
In contrast to the potential stimulatory effects on its own production, E2 might act in a classical negative feedback loop on ER activity through the down-regulation of many genes, the products of which are known to enhance ER activity. These would include SRC2, SRC3, TIF1, PNRC2, and SMAD3. In addition, as observed by others (41) and by us, E2 up-regulated the receptor corepressor RIP140. These observations are of particular interest because although the mechanisms of how coregulators function are being well studied, little is known about how coregulator expression is regulated. Overall, these findings suggest that E2 acts to alter levels of coregulators in a manner that would result in a decrease in ER activity, but whether this represents a classical negative feedback mechanism is not known. Alternatively, these changes could represent an overall change in the complement of cellular coregulators, leading to the preferential action of some coregulators over others. For example, the level of SRC1, which was not regulated by E2, would be increased in MCF-7 cells relative to the p160 steroid receptor coactivators SRC2/TIF2 and SRC3, both of which are down-regulated by E2 (57). Several recent studies have shown that the levels of coregulators, relative to one another, may dictate how a cell will respond to hormone. For example, the level of SRC1 in uterine cells is a critical determinant of how these cells respond to the SERM tamoxifen (12). Also, the balance between SRC1 and SRC2, which is down-regulated by E2, can determine peroxisome proliferator-activated receptor 
activity and adipogenesis in mice (58). Whether this down-regulation of important coactivators by E2 contributes to the E2-induced down-regulation of the numerous estrogen-responsive genes we have observed remains to be investigated.
In summary, our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to alter the proliferation and phenotype of breast cancer cells, and they demonstrate the very widespread effects of this hormone on breast cancer cells.
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Acknowledgments |
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Footnotes |
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Abbreviations: AP-1, Activating protein-1; BMP4, bone morphogenic protein 4; BTG, B cell translocation gene; CDC, cell division cycle; CHX, cycloheximide; CS, confidence score; E2, estradiol; ER, estrogen receptor; ERF, Ets2 repressor factor; HBP1, HMG box-containing protein 1; HMG, high-mobility group; MAD, mothers against decapentaplegic; MCM, minichromosome maintenance; NF-B, nuclear factor-B; PC3 pheochromacytoma cell-3; RFC4, replication factor C4; SDF-1, stromal cell-derived factor 1; SERM, selective ER modulator; SMAD3, Sma and MAD3; SRC, steroid receptor coactivator; TIF, transcriptional intermediary factor; TOB, transducer of ERBB2; VEGF, vascular endothelial growth factor.
Received May 7, 2003.
Accepted for publication July 1, 2003.
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F. Stossi, Z. Madak-Erdogan, and B. S. Katzenellenbogen Estrogen Receptor Alpha Represses Transcription of Early Target Genes via p300 and CtBP1 Mol. Cell. Biol., April 1, 2009; 29(7): 1749 - 1759. [Abstract] [Full Text] [PDF]
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D. Clements, S. L Asprey, T. A McCulloch, T. A Morris, S. A Watson, and S. R Johnson Analysis of the oestrogen response in an angiomyolipoma derived xenograft model Endocr. Relat. Cancer, March 1, 2009; 16(1): 59 - 72. [Abstract] [Full Text] [PDF]
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 P. Muller, K. W Merrell, J. D Crofts, C. Ronnlund, C.-Y. Lin, J.-A. Gustafsson, and A. Strom Estrogen-dependent downregulation of hairy and enhancer of split homolog-1 gene expression in breast cancer cells is mediated via a 3' distal element J. Endocrinol., March 1, 2009; 200(3): 311 - 319. [Abstract] [Full Text] [PDF]
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 F. Wu, I. Ivanov, R. Xu, and S. Safe Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies J. Mol. Endocrinol., January 1, 2009; 42(1): 19 - 33. [Abstract] [Full Text] [PDF]
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 S Badve and H Nakshatri Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications J. Clin. Pathol., January 1, 2009; 62(1): 6 - 12. [Abstract] [Full Text] [PDF]
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 J. Frasor, A. E. Weaver, M. Pradhan, and K. Mehta Synergistic Up-Regulation of Prostaglandin E Synthase Expression in Breast Cancer Cells by 17{beta}-Estradiol and Proinflammatory Cytokines Endocrinology, December 1, 2008; 149(12): 6272 - 6279. [Abstract] [Full Text] [PDF]
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 R. A. Stein, C.-y. Chang, D. A. Kazmin, J. Way, T. Schroeder, M. Wergin, M. W. Dewhirst, and D. P. McDonnell Estrogen-Related Receptor {alpha} Is Critical for the Growth of Estrogen Receptor-Negative Breast Cancer Cancer Res., November 1, 2008; 68(21): 8805 - 8812. [Abstract] [Full Text] [PDF]
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F. Wu, R. Xu, K. Kim, J. Martin, and S. Safe In Vivo Profiling of Estrogen Receptor/Specificity Protein-Dependent Transactivation Endocrinology, November 1, 2008; 149(11): 5696 - 5705. [Abstract] [Full Text] [PDF]
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Z. Madak-Erdogan, K. J. Kieser, S. H. Kim, B. Komm, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Nuclear and Extranuclear Pathway Inputs in the Regulation of Global Gene Expression by Estrogen Receptors Mol. Endocrinol., September 1, 2008; 22(9): 2116 - 2127. [Abstract] [Full Text] [PDF]
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G. M. Mager, R. M. Ward, R. Srinivasan, S.-W. Jang, L. Wrabetz, and J. Svaren Active Gene Repression by the Egr2{middle dot}NAB Complex during Peripheral Nerve Myelination J. Biol. Chem., June 27, 2008; 283(26): 18187 - 18197. [Abstract] [Full Text] [PDF]
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S. Raulic, Y. Ramos-Valdes, and G. E DiMattia Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro J. Endocrinol., June 1, 2008; 197(3): 517 - 529. [Abstract] [Full Text] [PDF]
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A. Boulay, M. Breuleux, C. Stephan, C. Fux, C. Brisken, M. Fiche, M. Wartmann, M. Stumm, H. A. Lane, and N. E. Hynes The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ER{alpha} Pathway in Breast Cancer Cancer Res., May 15, 2008; 68(10): 3743 - 3751. [Abstract] [Full Text] [PDF]
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B. Tan, X. Long, H. Nakshatri, K. P Nephew, and R. M Bigsby Striatin-3{gamma} inhibits estrogen receptor activity by recruiting a protein phosphatase J. Mol. Endocrinol., May 1, 2008; 40(5): 199 - 210. [Abstract] [Full Text] [PDF]
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X. Li, S. L Nott, Y. Huang, R. Hilf, R. A Bambara, X. Qiu, A. Yakovlev, S. Welle, and M. Muyan Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17{beta}-estradiol-estrogen receptor {beta} is uncoupled from the induction of phenotypic changes in cell models J. Mol. Endocrinol., May 1, 2008; 40(5): 211 - 229. [Abstract] [Full Text] [PDF]
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D. H. Barnett, S. Sheng, T. Howe Charn, A. Waheed, W. S. Sly, C.-Y. Lin, E. T. Liu, and B. S. Katzenellenbogen Estrogen Receptor Regulation of Carbonic Anhydrase XII through a Distal Enhancer in Breast Cancer Cancer Res., May 1, 2008; 68(9): 3505 - 3515. [Abstract] [Full Text] [PDF]
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E. C. Chang, T. H. Charn, S.-H. Park, W. G. Helferich, B. Komm, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen Receptors {alpha} and {beta} as Determinants of Gene Expression: Influence of Ligand, Dose, and Chromatin Binding Mol. Endocrinol., May 1, 2008; 22(5): 1032 - 1043. [Abstract] [Full Text] [PDF]
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 A. Kendall, H. Anderson, A. K. Dunbier, A. Mackay, T. Dexter, A. Urruticoechea, C. Harper-Wynne, and M. Dowsett Impact of Estrogen Deprivation on Gene Expression Profiles of Normal Postmenopausal Breast Tissue In vivo Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 855 - 863. [Abstract] [Full Text] [PDF]
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 G. Arpino, L. Wiechmann, C. K. Osborne, and R. Schiff Crosstalk between the Estrogen Receptor and the HER Tyrosine Kinase Receptor Family: Molecular Mechanism and Clinical Implications for Endocrine Therapy Resistance Endocr. Rev., April 1, 2008; 29(2): 217 - 233. [Abstract] [Full Text] [PDF]
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R. Dip, S. Lenz, J.-P. Antignac, B. Le Bizec, H. Gmuender, and H. Naegeli Global gene expression profiles induced by phytoestrogens in human breast cancer cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 161 - 173. [Abstract] [Full Text] [PDF]
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J.-M. Renoir, C. Bouclier, A. Seguin, V. Marsaud, and B. Sola Antioestrogen-mediated cell cycle arrest and apoptosis induction in breast cancer and multiple myeloma cells J. Mol. Endocrinol., March 1, 2008; 40(3): 101 - 112. [Abstract] [Full Text] [PDF]
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N. Levy, D. Tatomer, C. B. Herber, X. Zhao, H. Tang, T. Sargeant, L. J. Ball, J. Summers, T. P. Speed, and D. C. Leitman Differential Regulation of Native Estrogen Receptor-Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene Mol. Endocrinol., February 1, 2008; 22(2): 287 - 303. [Abstract] [Full Text] [PDF]
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K. J. Higgins, S. Liu, M. Abdelrahim, K. Vanderlaag, X. Liu, W. Porter, R. Metz, and S. Safe Vascular Endothelial Growth Factor Receptor-2 Expression Is Down-Regulated by 17{beta}-Estradiol in MCF-7 Breast Cancer Cells by Estrogen Receptor {alpha}/Sp Proteins Mol. Endocrinol., February 1, 2008; 22(2): 388 - 402. [Abstract] [Full Text] [PDF]
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V. Bourdeau, J. Deschenes, D. Laperriere, M. Aid, J. H. White, and S. Mader Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells Nucleic Acids Res., January 17, 2008; 36(1): 76 - 93. [Abstract] [Full Text] [PDF]
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 E. Carreras, S. Turner, V. Paharkova-Vatchkova, A. Mao, C. Dascher, and S. Kovats Estradiol Acts Directly on Bone Marrow Myeloid Progenitors to Differentially Regulate GM-CSF or Flt3 Ligand-Mediated Dendritic Cell Differentiation J. Immunol., January 15, 2008; 180(2): 727 - 738. [Abstract] [Full Text] [PDF]
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C. C Valley, N. M Solodin, G. L Powers, S. J Ellison, and E. T Alarid Temporal variation in estrogen receptor-{alpha} protein turnover in the presence of estrogen J. Mol. Endocrinol., January 1, 2008; 40(1): 23 - 34. [Abstract] [Full Text] [PDF]
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C. D. DuSell, M. Umetani, P. W. Shaul, D. J. Mangelsdorf, and D. P. McDonnell 27-Hydroxycholesterol Is an Endogenous Selective Estrogen Receptor Modulator Mol. Endocrinol., January 1, 2008; 22(1): 65 - 77. [Abstract] [Full Text] [PDF]
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J. X. Zou, A. S. Revenko, L. B. Li, A. T. Gemo, and H.-W. Chen ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ER{alpha}, is required for coregulator occupancy and chromatin modification PNAS, November 13, 2007; 104(46): 18067 - 18072. [Abstract] [Full Text] [PDF]
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J. C. Harrell, W. W. Dye, D. M.E. Harvell, M. Pinto, P. Jedlicka, C. A. Sartorius, and K. B. Horwitz Estrogen Insensitivity in a Model of Estrogen Receptor Positive Breast Cancer Lymph Node Metastasis Cancer Res., November 1, 2007; 67(21): 10582 - 10591. [Abstract] [Full Text] [PDF]
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J. Sun, Z. Nawaz, and J. M. Slingerland Long-Range Activation of GREB1 by Estrogen Receptor via Three Distal Consensus Estrogen-Responsive Elements in Breast Cancer Cells Mol. Endocrinol., November 1, 2007; 21(11): 2651 - 2662. [Abstract] [Full Text] [PDF]
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 X.-F. Le, A. S. Arachchige-Don, W. Mao, M. C. Horne, and R. C. Bast Jr. Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells Mol. Cancer Ther., November 1, 2007; 6(11): 2843 - 2857. [Abstract] [Full Text] [PDF]
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J. Cheng, C. Zhang, and D. J. Shapiro A Functional Serine 118 Phosphorylation Site in Estrogen Receptor-{alpha} Is Required for Down-Regulation of Gene Expression by 17{beta}-Estradiol and 4-Hydroxytamoxifen Endocrinology, October 1, 2007; 148(10): 4634 - 4641. [Abstract] [Full Text] [PDF]
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J. E Burdette and T. K Woodruff Activin and estrogen crosstalk regulates transcription in human breast cancer cells Endocr. Relat. Cancer, September 1, 2007; 14(3): 679 - 689. [Abstract] [Full Text] [PDF]
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J. D. Stender, J. Frasor, B. Komm, K. C. N. Chang, W. L. Kraus, and B. S. Katzenellenbogen Estrogen-Regulated Gene Networks in Human Breast Cancer Cells: Involvement of E2F1 in the Regulation of Cell Proliferation Mol. Endocrinol., September 1, 2007; 21(9): 2112 - 2123. [Abstract] [Full Text] [PDF]
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Y. Drabsch, H. Hugo, R. Zhang, D. H. Dowhan, Y. R. Miao, A. M. Gewirtz, S. C. Barry, R. G. Ramsay, and T. J. Gonda Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells PNAS, August 21, 2007; 104(34): 13762 - 13767. [Abstract] [Full Text] [PDF]
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A. Sayeed, S. D. Konduri, W. Liu, S. Bansal, F. Li, and G. M. Das Estrogen Receptor {alpha} Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis Cancer Res., August 15, 2007; 67(16): 7746 - 7755. [Abstract] [Full Text] [PDF]
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 K. Mita, Z. Zhang, Y. Ando, T. Toyama, M. Hamaguchi, S. Kobayashi, S.-i. Hayashi, Y. Fujii, H. Iwase, and H. Yamashita Prognostic Significance of Insulin-like Growth Factor Binding Protein (IGFBP)-4 and IGFBP-5 Expression in Breast Cancer Jpn. J. Clin. Oncol., August 3, 2007; (2007) hym066v1. [Abstract] [Full Text] [PDF]
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J. R. Schultz-Norton, V. A. Gabisi, Y. S. Ziegler, I. X. McLeod, J. R. Yates, and A. M. Nardulli Interaction of estrogen receptor {alpha} with proliferating cell nuclear antigen Nucleic Acids Res., August 1, 2007; 35(15): 5028 - 5038. [Abstract] [Full Text] [PDF]
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M. Kininis, B. S. Chen, A. G. Diehl, G. D. Isaacs, T. Zhang, A. C. Siepel, A. G. Clark, and W. L. Kraus Genomic Analyses of Transcription Factor Binding, Histone Acetylation, and Gene Expression Reveal Mechanistically Distinct Classes of Estrogen-Regulated Promoters Mol. Cell. Biol., July 15, 2007; 27(14): 5090 - 5104. [Abstract] [Full Text] [PDF]
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J. R. Schultz-Norton, K. A. Walt, Y. S. Ziegler, I. X. McLeod, J. R. Yates, L. T. Raetzman, and A. M. Nardulli The Deoxyribonucleic Acid Repair Protein Flap Endonuclease-1 Modulates Estrogen-Responsive Gene Expression Mol. Endocrinol., July 1, 2007; 21(7): 1569 - 1580. [Abstract] [Full Text] [PDF]
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N. Levy, X. Zhao, H. Tang, R. B. Jaffe, T. P. Speed, and D. C. Leitman Multiple Transcription Factor Elements Collaborate with Estrogen Receptor {alpha} to Activate an Inducible Estrogen Response Element in the NKG2E Gene Endocrinology, July 1, 2007; 148(7): 3449 - 3458. [Abstract] [Full Text] [PDF]
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 S. Lee, D. Medina, A. Tsimelzon, S. K. Mohsin, S. Mao, Y. Wu, and D. C. Allred Alterations of Gene Expression in the Development of Early Hyperplastic Precursors of Breast Cancer Am. J. Pathol., July 1, 2007; 171(1): 252 - 262. [Abstract] [Full Text] [PDF]
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J. Deschenes, V. Bourdeau, J. H. White, and S. Mader Regulation of GREB1 Transcription by Estrogen Receptor {alpha} through a Multipartite Enhancer Spread Over 20 kb of Upstream Flanking Sequences J. Biol. Chem., June 15, 2007; 282(24): 17335 - 17339. [Abstract] [Full Text] [PDF]
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S. M Johnson, M. Maleki-Dizaji, J. A Styles, and I. N H White Ishikawa cells exhibit differential gene expression profiles in response to oestradiol or 4-hydroxytamoxifen Endocr. Relat. Cancer, June 1, 2007; 14(2): 337 - 350. [Abstract] [Full Text] [PDF]
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J. L. Kipp, S. M. Kilen, S. Bristol-Gould, T. K. Woodruff, and K. E. Mayo Neonatal Exposure to Estrogens Suppresses Activin Expression and Signaling in the Mouse Ovary Endocrinology, May 1, 2007; 148(5): 1968 - 1976. [Abstract] [Full Text] [PDF]
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 Y.-L. Lo, J.-C. Yu, S.-T. Chen, G.-C. Hsu, Y.-C. Mau, S.-L. Yang, P.-E. Wu, and C.-Y. Shen Breast cancer risk associated with genotypic polymorphism of the mitotic checkpoint genes: a multigenic study on cancer susceptibility Carcinogenesis, May 1, 2007; 28(5): 1079 - 1086. [Abstract] [Full Text] [PDF]
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Y.-S. Kwon, I. Garcia-Bassets, K. R. Hutt, C. S. Cheng, M. Jin, D. Liu, C. Benner, D. Wang, Z. Ye, M. Bibikova, et al. Sensitive ChIP-DSL technology reveals an extensive estrogen receptor {alpha}-binding program on human gene promoters PNAS, March 20, 2007; 104(12): 4852 - 4857. [Abstract] [Full Text] [PDF]
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 R. W. Li, M. J. Meyer, Curtis. P. Van Tassell, T. S. Sonstegard, E. E. Connor, M. E. Van Amburgh, Y. R. Boisclair, and A. V. Capuco Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis Physiol Genomics, January 12, 2007; 27(1): 42 - 53. [Abstract] [Full Text] [PDF]
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M. Fan, P. S. Yan, C. Hartman-Frey, L. Chen, H. Paik, S. L. Oyer, J. D. Salisbury, A. S.L. Cheng, L. Li, P. H. Abbosh, et al. Diverse Gene Expression and DNA Methylation Profiles Correlate with Differential Adaptation of Breast Cancer Cells to the Antiestrogens Tamoxifen and Fulvestrant Cancer Res., December 15, 2006; 66(24): 11954 - 11966. [Abstract] [Full Text] [PDF]
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J. Lopez-Garcia, M. Periyasamy, R. S. Thomas, M. Christian, M. Leao, P. Jat, K. B. Kindle, D. M. Heery, M. G. Parker, L. Buluwela, et al. ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases Nucleic Acids Res., December 4, 2006; 34(21): 6126 - 6136. [Abstract] [Full Text] [PDF]
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S Tozlu, I Girault, S Vacher, J Vendrell, C Andrieu, F Spyratos, P Cohen, R Lidereau, and I Bieche Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach Endocr. Relat. Cancer, December 1, 2006; 13(4): 1109 - 1120. [Abstract] [Full Text] [PDF]
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J M W Gee, V E Shaw, S E Hiscox, R A McClelland, N K Rushmere, and R I Nicholson Deciphering antihormone-induced compensatory mechanisms in breast cancer and their therapeutic implications Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S77 - S88. [Abstract] [Full Text] [PDF]
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J. Hur, D. W. Bell, K. L. Dean, K. R. Coser, P. C. Hilario, R. A. Okimoto, E. M. Tobey, S. L. Smith, K. J. Isselbacher, and T. Shioda Regulation of Expression of BIK Proapoptotic Protein in Human Breast Cancer Cells: p53-Dependent Induction of BIK mRNA by Fulvestrant and Proteasomal Degradation of BIK Protein. Cancer Res., October 15, 2006; 66(20): 10153 - 10161. [Abstract] [Full Text] [PDF]
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E. C. Chang, J. Frasor, B. Komm, and B. S. Katzenellenbogen Impact of Estrogen Receptor {beta} on Gene Networks Regulated by Estrogen Receptor {alpha} in Breast Cancer Cells Endocrinology, October 1, 2006; 147(10): 4831 - 4842. [Abstract] [Full Text] [PDF]
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K. D. Salazar, M. R. Miller, J. B. Barnett, and R. Schafer Evidence for a Novel Endocrine Disruptor: The Pesticide Propanil Requires the Ovaries and Steroid Synthesis to Enhance Humoral Immunity Toxicol. Sci., September 1, 2006; 93(1): 62 - 74. [Abstract] [Full Text] [PDF]
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 C. R. Montague, M. G. Hunter, M. A. Gavrilin, G. S. Phillips, P. J. Goldschmidt-Clermont, and C. B. Marsh Activation of Estrogen Receptor-{alpha} Reduces Aortic Smooth Muscle Differentiation Circ. Res., September 1, 2006; 99(5): 477 - 484. [Abstract] [Full Text] [PDF]
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T. Shioda, J. Chesnes, K. R. Coser, L. Zou, J. Hur, K. L. Dean, C. Sonnenschein, A. M. Soto, and K. J. Isselbacher Importance of dosage standardization for interpreting transcriptomal signature profiles: Evidence from studies of xenoestrogens PNAS, August 8, 2006; 103(32): 12033 - 12038. [Abstract] [Full Text] [PDF]
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J. S. Carroll and M. Brown Estrogen Receptor Target Gene: An Evolving Concept Mol. Endocrinol., August 1, 2006; 20(8): 1707 - 1714. [Abstract] [Full Text] [PDF]
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 Y. C. Lim, L. Li, Z. Desta, Q. Zhao, J. M. Rae, D. A. Flockhart, and T. C. Skaar Endoxifen, a Secondary Metabolite of Tamoxifen, and 4-OH-Tamoxifen Induce Similar Changes in Global Gene Expression Patterns in MCF-7 Breast Cancer Cells J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 503 - 512. [Abstract] [Full Text] [PDF]
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W. R. Harrington, S. Sengupta, and B. S. Katzenellenbogen Estrogen Regulation of the Glucuronidation Enzyme UGT2B15 in Estrogen Receptor-Positive Breast Cancer Cells Endocrinology, August 1, 2006; 147(8): 3843 - 3850. [Abstract] [Full Text] [PDF]
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T. Buterin, C. Koch, and H. Naegeli Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells Carcinogenesis, August 1, 2006; 27(8): 1567 - 1578. [Abstract] [Full Text] [PDF]
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J. Frasor, E. C. Chang, B. Komm, C.-Y. Lin, V. B. Vega, E. T. Liu, L. D. Miller, J. Smeds, J. Bergh, and B. S. Katzenellenbogen Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res., July 15, 2006; 66(14): 7334 - 7340. [Abstract] [Full Text] [PDF]
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L. A. Helguero, M. Hedengran Faulds, C. Forster, J.-A. Gustafsson, and L.-A. Haldosen DAX-1 Expression Is Regulated during Mammary Epithelial Cell Differentiation Endocrinology, July 1, 2006; 147(7): 3249 - 3259. [Abstract] [Full Text] [PDF]
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F. Stossi, V. S. Likhite, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen-occupied Estrogen Receptor Represses Cyclin G2 Gene Expression and Recruits a Repressor Complex at the Cyclin G2 Promoter J. Biol. Chem., June 16, 2006; 281(24): 16272 - 16278. [Abstract] [Full Text] [PDF]
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C L Wilson, A H Sims, A Howell, C J Miller, and R B Clarke Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. Endocr. Relat. Cancer, June 1, 2006; 13(2): 617 - 628. [Abstract] [Full Text] [PDF]
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W. Liu, S. D. Konduri, S. Bansal, B. K. Nayak, S. A. Rajasekaran, S. M. Karuppayil, A. K. Rajasekaran, and G. M. Das Estrogen Receptor-{alpha} Binds p53 Tumor Suppressor Protein Directly and Represses Its Function J. Biol. Chem., April 14, 2006; 281(15): 9837 - 9840. [Abstract] [Full Text] [PDF]
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W. R. Harrington, S. H. Kim, C. C. Funk, Z. Madak-Erdogan, R. Schiff, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen Dendrimer Conjugates that Preferentially Activate Extranuclear, Nongenomic Versus Genomic Pathways of Estrogen Action Mol. Endocrinol., March 1, 2006; 20(3): 491 - 502. [Abstract] [Full Text] [PDF]
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D. M. E. Harvell, J. K. Richer, D. C. Allred, C. A. Sartorius, and K. B. Horwitz Estradiol Regulates Different Genes in Human Breast Tumor Xenografts Compared with the Identical Cells in Culture Endocrinology, February 1, 2006; 147(2): 700 - 713. [Abstract] [Full Text] [PDF]
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 E. Attar and S.E. Bulun Aromatase and other steroidogenic genes in endometriosis: translational aspects Hum. Reprod. Update, January 1, 2006; 12(1): 49 - 56. [Abstract] [Full Text] [PDF]
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T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]
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N. Normanno, M. Di Maio, E. De Maio, A. De Luca, A. de Matteis, A. Giordano, F. Perrone, and on behalf of the NCI-Naples Breast Cancer Group Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 721 - 747. [Abstract] [Full Text] [PDF]
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 O. Imamov, G.-J. Shim, M. Warner, and J.-A. Gustafsson Estrogen Receptor beta in Health and Disease Biol Reprod, November 1, 2005; 73(5): 866 - 871. [Abstract] [Full Text] [PDF]
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V X Jin, H Sun, T T Pohar, S Liyanarachchi, S K Palaniswamy, T H-M Huang, and R V Davuluri ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes J. Mol. Endocrinol., October 1, 2005; 35(2): 225 - 230. [Abstract] [Full Text] [PDF]
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H. Kishimoto, Z. Wang, P. Bhat-Nakshatri, D. Chang, R. Clarke, and H. Nakshatri The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1{alpha}/CXCL12 Carcinogenesis, October 1, 2005; 26(10): 1706 - 1715. [Abstract] [Full Text] [PDF]
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J. Frasor, J. M. Danes, C. C. Funk, and B. S. Katzenellenbogen Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes PNAS, September 13, 2005; 102(37): 13153 - 13157. [Abstract] [Full Text] [PDF]
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 S. E. Bulun, Z. Lin, G. Imir, S. Amin, M. Demura, B. Yilmaz, R. Martin, H. Utsunomiya, S. Thung, B. Gurates, et al. Regulation of Aromatase Expression in Estrogen-Responsive Breast and Uterine Disease: From Bench to Treatment Pharmacol. Rev., September 1, 2005; 57(3): 359 - 383. [Abstract] [Full Text] [PDF]
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J. Laganiere, G. Deblois, C. Lefebvre, A. R. Bataille, F. Robert, and V. Giguere From the Cover: Location analysis of estrogen receptor {alpha} target promoters reveals that FOXA1 defines a domain of the estrogen response PNAS, August 16, 2005; 102(33): 11651 - 11656. [Abstract] [Full Text] [PDF]
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E. Peeva, J. Venkatesh, and B. Diamond Tamoxifen Blocks Estrogen-Induced B Cell Maturation but Not Survival J. Immunol., August 1, 2005; 175(3): 1415 - 1423. [Abstract] [Full Text] [PDF]
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Y. Yamaguchi, H. Takei, K. Suemasu, Y. Kobayashi, M. Kurosumi, N. Harada, and S.-i. Hayashi Tumor-Stromal Interaction through the Estrogen-Signaling Pathway in Human Breast Cancer Cancer Res., June 1, 2005; 65(11): 4653 - 4662. [Abstract] [Full Text] [PDF]
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J. Laganiere, G. Deblois, and V. Giguere Functional Genomics Identifies a Mechanism for Estrogen Activation of the Retinoic Acid Receptor {alpha}1 Gene in Breast Cancer Cells Mol. Endocrinol., June 1, 2005; 19(6): 1584 - 1592. [Abstract] [Full Text] [PDF]
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D. Rai, A. Frolova, J. Frasor, A. E. Carpenter, and B. S. Katzenellenbogen Distinctive Actions of Membrane-Targeted Versus Nuclear Localized Estrogen Receptors in Breast Cancer Cells Mol. Endocrinol., June 1, 2005; 19(6): 1606 - 1617. [Abstract] [Full Text] [PDF]
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E. R. Simpson, M. Misso, K. N. Hewitt, R. A. Hill, W. C. Boon, M. E. Jones, A. Kovacic, J. Zhou, and C. D. Clyne Estrogen--the Good, the Bad, and the Unexpected Endocr. Rev., May 1, 2005; 26(3): 322 - 330. [Full Text] [PDF]
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J G Moggs, T C Murphy, F L Lim, D J Moore, R Stuckey, K Antrobus, I Kimber, and G Orphanides Anti-proliferative effect of estrogen in breast cancer cells that re-express ER{alpha} is mediated by aberrant regulation of cell cycle genes J. Mol. Endocrinol., April 1, 2005; 34(2): 535 - 551. [Abstract] [Full Text] [PDF]
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