| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cell Line LNCaP Involves Reduction of Cyclin-Dependent Kinase 2 Activity and Persistent G1 Accumulation
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33136
Address all correspondence and requests for reprints to: Kerry L. Burnstein, Department of Molecular and Cellular Pharmacology (R-189), University of Miami School of Medicine, P.O. Box 016189, Miami, Florida 33101. E-mail: kburnste{at}molbio.med.miami.edu
1
,25-Dihydroxyvitamin D3 (1,25 D), the most active
metabolite of vitamin D3, exerts antiproliferative and
prodifferentiating effects on some human prostate cancer cell lines. We
previously reported an inverse relationship between functional vitamin
D receptor (VDR) levels and antiproliferative response to 1,25 D in two
human prostate cancer cell lines, LNCaP and ALVA 31. Although LNCaP
cells are far more sensitive to growth inhibition by 1,25 D than ALVA
31 cells, LNCaP express approximately half the number of VDR as ALVA
31. Two other human prostate cancer cell lines studied, PC3 and DU145,
express lower levels of functional VDR and are relatively insensitive
to growth inhibition by 1,25 D. In this report, we investigated
potential mechanisms of the variable antiproliferative activity of 1,25
D. In PC3 cells stably expressing VDR [PC3(VDR)] at levels comparable
to LNCaP, 1,25 D treatment resulted in only moderate growth inhibition.
These results further support the contention that VDR expression,
although required, is not sufficient for maximal growth suppression by
1,25 D, as is exhibited by LNCaP cells. We did not detect 1,25
D-mediated DNA fragmentation after 4 days of 1,25 D treatment in either
LNCaP or ALVA 31 cells. This result suggests that variability in 1,25 D
sensitivity does not derive from differences in the capacity of these
cells to undergo apoptosis in response to 1,25 D. Flow cytometry of
propidium iodine-stained cells revealed that 48 h 1,25 D treatment
of LNCaP cells resulted in a 2-fold decrease of cells in G2/M plus S
phases and accumulation of LNCaP cells in the G1/G0 phase. This effect
persisted for 72 h after 1,25 D removal. In contrast, 1,25 D did
not significantly alter the cell cycle distribution of ALVA 31 or
PC3(VDR) cells. Consistent with accumulation of cells in G1/G0, 1,25 D
treatment of LNCaP cells resulted in decreased retinoblastoma protein
phosphorylation, repressed E2F transcriptional activity, increased
levels of the cyclin-dependent kinase (CDK) inhibitor
p21WAF1, CIP1, and decreased CDK2 activity.
However, p21 messenger RNA levels were not altered, suggesting
translational or posttranslational regulation of p21 by 1,25 D. In
contrast, p21 was not detected in ALVA 31 or PC3(VDR) and was not
induced by 1,25 D, consistent with the failure of 1,25 D to influence
cell cycle distribution in these cells. These results suggest that
variability in sensitivity to the antiproliferative effects of 1,25 D
among prostate cancer cells is dependent, at least in part, on the
integrity of the retinoblastoma pathway and in particular on p21
expression and 1,25 D regulation of CDK2 activity.
This article has been cited by other articles:
 |
|
 |
|
  M. Jenab, J. McKay, H. B. Bueno-de-Mesquita, F. J.B. van Duijnhoven, P. Ferrari, N. Slimani, E. H.J.M. Jansen, T. Pischon, S. Rinaldi, A. Tjonneland, et al. Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations Cancer Epidemiol. Biomarkers Prev., September 1, 2009; 18(9): 2485 - 2491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. THILL, D. FISCHER, S. BECKER, T. CORDES, C. DITTMER, K. DIEDRICH, D. SALEHIN, and M. FRIEDRICH Prostaglandin Metabolizing Enzymes in Correlation with Vitamin D Receptor in Benign and Malignant Breast Cell Lines Anticancer Res, September 1, 2009; 29(9): 3619 - 3625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. P. Rohan and N. L. Weigel 1{alpha},25-Dihydroxyvitamin D3 Reduces c-Myc Expression, Inhibiting Proliferation and Causing G1 Accumulation in C4-2 Prostate Cancer Cells Endocrinology, May 1, 2009; 150(5): 2046 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chung, A. R. Karpf, J. R. Muindi, J. M. Conroy, N. J. Nowak, C. S. Johnson, and D. L. Trump Epigenetic Silencing of CYP24 in Tumor-derived Endothelial Cells Contributes to Selective Growth Inhibition by Calcitriol J. Biol. Chem., March 23, 2007; 282(12): 8704 - 8714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chung, M. K. Wong, G. Flynn, W.-d. Yu, C. S. Johnson, and D. L. Trump Differential Antiproliferative Effects of Calcitriol on Tumor-Derived and Matrigel-Derived Endothelial Cells. Cancer Res., September 1, 2006; 66(17): 8565 - 8573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Moreno, A. V. Krishnan, S. Swami, L. Nonn, D. M. Peehl, and D. Feldman Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells Cancer Res., September 1, 2005; 65(17): 7917 - 7925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. M. Sutton, X. Zhang, T. I. Ellison, and P. N. MacDonald The 1,25(OH)2D3-Regulated Transcription Factor MN1 Stimulates Vitamin D Receptor-Mediated Transcription and Inhibits Osteoblastic Cell Proliferation Mol. Endocrinol., September 1, 2005; 19(9): 2234 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P Dwivedi, P. H Anderson, J. L Omdahl, H L. Grimes, H. A Morris, and B. K May Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells Endocr. Relat. Cancer, June 1, 2005; 12(2): 351 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikezoe, S. Gery, D. Yin, J. O'Kelly, L. Binderup, N. Lemp, H. Taguchi, and H. P. Koeffler CCAAT/Enhancer-Binding Protein {delta}: A Molecular Target of 1,25-Dihydroxyvitamin D3 in Androgen-Responsive Prostate Cancer LNCaP Cells Cancer Res., June 1, 2005; 65(11): 4762 - 4768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mukherjee and S. E. Conrad c-Myc Suppresses p21WAF1/CIP1 Expression during Estrogen Signaling and Antiestrogen Resistance in Human Breast Cancer Cells J. Biol. Chem., May 6, 2005; 280(18): 17617 - 17625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-C. Li, P. R. Carroll, and R. Dahiya Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment J Natl Cancer Inst, January 19, 2005; 97(2): 103 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Swamy, T. C. Chen, S. Peleg, P. Dhawan, S. Christakos, L. V. Stewart, N. L. Weigel, R. G. Mehta, M. F. Holick, and R. Ray Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3{beta}-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells Clin. Cancer Res., December 1, 2004; 10(23): 8018 - 8027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Foley, D. Hollywood, and M. Lawler Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease Endocr. Relat. Cancer, September 1, 2004; 11(3): 477 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang, R. Nahta, G. Huper, and J. R. Marks TAFII70 Isoform-Specific Growth Suppression Correlates With Its Ability to Complex With the GADD45a Protein Mol. Cancer Res., August 1, 2004; 2(8): 442 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Peng, P. J. Malloy, and D. Feldman Identification of a Functional Vitamin D Response Element in the Human Insulin-Like Growth Factor Binding Protein-3 Promoter Mol. Endocrinol., May 1, 2004; 18(5): 1109 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Stewart and N. L. Weigel Vitamin D and Prostate Cancer Experimental Biology and Medicine, April 1, 2004; 229(4): 277 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ohkawa, H. Ishida, F. Nakanishi, A. Hosui, K. Ueda, T. Takehara, M. Hori, and N. Hayashi Hepatitis C Virus Core Functions as a Suppressor of Cyclin-dependent Kinase-activating Kinase and Impairs Cell Cycle Progression J. Biol. Chem., March 19, 2004; 279(12): 11719 - 11726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rao, A. Coan, J.-E. Welsh, W. W. Barclay, C. Koumenis, and S. D. Cramer Vitamin D Receptor and p21/WAF1 Are Targets of Genistein and 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer Cells Cancer Res., March 15, 2004; 64(6): 2143 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Beer and A. Myrthue Calcitriol in cancer treatment: From the lab to the clinic Mol. Cancer Ther., March 1, 2004; 3(3): 373 - 381. [Abstract] [Full Text]
|
|
|
|
|
|
E. S. Yang and K. L. Burnstein Vitamin D Inhibits G1 to S Progression in LNCaP Prostate Cancer Cells through p27Kip1 Stabilization and Cdk2 Mislocalization to the Cytoplasm J. Biol. Chem., November 21, 2003; 278(47): 46862 - 46868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Polek, L. V. Stewart, E. J. Ryu, M. B. Cohen, E. A. Allegretto, and N. L. Weigel p53 Is Required for 1,25-Dihydroxyvitamin D3-Induced G0 Arrest But Is Not Required for G1 Accumulation or Apoptosis of LNCaP Prostate Cancer Cells Endocrinology, January 1, 2003; 144(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Galbiati, L. Polastri, S. Gregori, M. Freschi, M. Casorati, U. Cavallaro, P. Fiorina, F. Bertuzzi, A. Zerbi, G. Pozza, et al. Antitumorigenic and Antiinsulinogenic Effects of Calcitriol on Insulinoma Cells and Solid {beta}-Cell Tumors Endocrinology, October 1, 2002; 143(10): 4018 - 4030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. N. Wade, M. C. Willingham, C. Koumenis, and S. D. Cramer p27Kip1 Is Essential for the Antiproliferative Action of 1,25-Dihydroxyvitamin D3 in Primary, but Not Immortalized, Mouse Embryonic Fibroblasts J. Biol. Chem., September 27, 2002; 277(40): 37301 - 37306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goodin, K. V. Rao, and R. S. DiPaola State-of-the-Art Treatment of Metastatic Hormone-Refractory Prostate Cancer Oncologist, August 1, 2002; 7(4): 360 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Lin, Y. Nagai, R. Sladek, Y. Bastien, J. Ho, K. Petrecca, G. Sotiropoulou, E. P. Diamandis, T. J. Hudson, and J. H. White Expression Profiling in Squamous Carcinoma Cells Reveals Pleiotropic Effects of Vitamin D3 Analog EB1089 Signaling on Cell Proliferation, Differentiation, and Immune System Regulation Mol. Endocrinol., June 1, 2002; 16(6): 1243 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Prufer, C. Schroder, K. Hegyi, and J. Barsony Degradation of RXRs Influences Sensitivity of Rat Osteosarcoma Cells to the Antiproliferative Effects of Calcitriol Mol. Endocrinol., May 1, 2002; 16(5): 961 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Moffatt, W. U. Johannes, T. E. Hedlund, and G. J. Miller Growth Inhibitory Effects of 1{alpha}, 25-Dihydroxyvitamin D3 Are Mediated by Increased Levels of p21 in the Prostatic Carcinoma Cell Line ALVA-31 Cancer Res., October 1, 2001; 61(19): 7122 - 7129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Jensen, M. W. Madsen, J. Lukas, L. Binderup, and J. Bartek Inhibitory Effects of 1{alpha},25-Dihydroxyvitamin D3 on the G1-S Phase-Controlling Machinery Mol. Endocrinol., August 1, 2001; 15(8): 1370 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Akutsu, R. Lin, Y. Bastien, A. Bestawros, D. J. Enepekides, M. J. Black, and J. H. White Regulation of Gene Expression by 1{{alpha}},25-Dihydroxyvitamin D3 and Its Analog EB1089 under Growth-Inhibitory Conditions in Squamous Carcinoma Cells Mol. Endocrinol., July 1, 2001; 15(7): 1127 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Prudencio, N. Akutsu, N. Benlimame, T. Wang, Y. Bastien, R. Lin, M. J. Black, M. A. Alaoui-Jamali, and J. H. White Action of Low Calcemic 1{{alpha}},25-Dihydroxyvitamin D3 Analogue EB1089 in Head and Neck Squamous Cell Carcinoma J Natl Cancer Inst, May 16, 2001; 93(10): 745 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Hershberger, W.-D. Yu, R. A. Modzelewski, R. M. Rueger, C. S. Johnson, and D. L. Trump Calcitriol (1,25-Dihydroxycholecalciferol) Enhances Paclitaxel Antitumor Activity in Vitro and in Vivo and Accelerates Paclitaxel-induced Apoptosis Clin. Cancer Res., April 1, 2001; 7(4): 1043 - 1051. [Abstract] [Full Text]
|
|
|
|
|
|
B. A. Scaglione-Sewell, M. Bissonnette, S. Skarosi, C. Abraham, and T. A. Brasitus A Vitamin D3 Analog Induces a G1-Phase Arrest in CaCo-2 Cells by Inhibiting Cdk2 and Cdk6: Roles of Cyclin E, p21Waf1, and p27Kip1 Endocrinology, November 1, 2000; 141(11): 3931 - 3939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Zhao, D. M. Peehl, N. M. Navone, and D. Feldman 1{alpha},25-Dihydroxyvitamin D3 Inhibits Prostate Cancer Cell Growth by Androgen-Dependent and Androgen-Independent Mechanisms Endocrinology, July 1, 2000; 141(7): 2548 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Qadan, C. M. Perez-Stable, R. H. Schwall, K. L. Burnstein, R. C. Ostenson, G. A. Howard, and B. A. Roos Hepatocyte Growth Factor and Vitamin D Cooperatively Inhibit Androgen-Unresponsive Prostate Cancer Cell Lines Endocrinology, July 1, 2000; 141(7): 2567 - 2573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Chen, G. G. Schwartz, K. L. Burnstein, B. L. Lokeshwar, and M. F. Holick The in Vitro Evaluation of 25-Hydroxyvitamin D3 and 19-nor-1{{alpha}},25-Dihydroxyvitamin D2 as Therapeutic Agents for Prostate Cancer Clin. Cancer Res., March 1, 2000; 6(3): 901 - 908. [Abstract] [Full Text]
|
|
|
|
|
|
S. E. Blutt, T. C. Polek, L. V. Stewart, M. W. Kattan, and N. L. Weigel A Calcitriol Analogue, EB1089, Inhibits the Growth of LNCaP Tumors in Nude Mice Cancer Res., February 1, 2000; 60(4): 779 - 782. [Abstract] [Full Text]
|
|
|
|
|
|
D. Feldman, X.-Y. Zhao, and A. V. Krishnan Editorial/Mini-Review: Vitamin D and Prostate Cancer Endocrinology, January 1, 2000; 141(1): 5 - 9. [Full Text] [PDF]
|
|
|
|
|
|
S. E. Blutt, T. J. McDonnell, T. C. Polek, and N. L. Weigel Calcitriol-Induced Apoptosis in LNCaP Cells Is Blocked By Overexpression of Bcl-2 Endocrinology, January 1, 2000; 141(1): 10 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Habuchi, T. Suzuki, R. Sasaki, L. Wang, K. Sato, S. Satoh, T. Akao, N. Tsuchiya, N. Shimoda, Y. Wada, et al. Association of Vitamin D Receptor Gene Polymorphism with Prostate Cancer and Benign Prostatic Hyperplasia in a Japanese Population Cancer Res., January 1, 2000; 60(2): 305 - 308. [Abstract] [Full Text]
|
|
|
|
|
|
P. A. Hershberger, R. A. Modzelewski, Z. R. Shurin, R. M. Rueger, D. L. Trump, and C. S. Johnson 1,25-Dihydroxycholecalciferol (1,25-D3) Inhibits the Growth of Squamous Cell Carcinoma and Down-Modulates p21Waf1/Cip1 in Vitro and in Vivo Cancer Res., June 1, 1999; 59(11): 2644 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Ly, X.-Y. Zhao, L. Holloway, and D. Feldman Liarozole Acts Synergistically with 1{alpha},25-Dihydroxyvitamin D3 to Inhibit Growth of DU 145 Human Prostate Cancer Cells by Blocking 24-Hydroxylase Activity Endocrinology, May 1, 1999; 140(5): 2071 - 2076. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. J Medina, R. S DiPaola, and S. Goodin Treatment of hormone-refractory prostate cancer Journal of Oncology Pharmacy Practice, March 1, 1999; 5(1): 32 - 48. [Abstract] [PDF]
|
|
|
|
|
|
X.-Y. Zhao, L. H. Ly, D. M. Peehl, and D. Feldman Induction of Androgen Receptor by 1{alpha},25-Dihydroxyvitamin D3 and 9-cis Retinoic Acid in LNCaP Human Prostate Cancer Cells Endocrinology, March 1, 1999; 140(3): 1205 - 1212. [Abstract] [Full Text]
|
|
|
|
|
|
K. A. Moffatt, W. U. Johannes, and G. J. Miller 1{{alpha}},25-Dihydroxyvitamin D3 and Platinum Drugs Act Synergistically to Inhibit the Growth of Prostate Cancer Cell Lines Clin. Cancer Res., March 1, 1999; 5(3): 695 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text]
|
|
|
|
|
|
T. F. McGuire, D. L. Trump, and C. S. Johnson Vitamin D3-induced Apoptosis of Murine Squamous Cell Carcinoma Cells. SELECTIVE INDUCTION OF CASPASE-DEPENDENT MEK CLEAVAGE AND UP-REGULATION OF MEKK-1 J. Biol. Chem., July 6, 2001; 276(28): 26365 - 26373. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
