Endocrinology Vol. 141, No. 9 3194-3199
Copyright © 2000 by The Endocrine Society
Androgen-Regulated Expression of a Novel Member of the Aldo-Keto Reductase Superfamily in Regrowing Rat Prostate1
Nozomu Nishi,
Hiroki Shoji,
Hiroshi Miyanaka and
Takanori Nakamura
Department of Endocrinology (N.N., H.S., T.N.) and Research
Equipment Center (H.M.), Faculty of Medicine, Kagawa Medical
University, Kagawa 761-0793, Japan
Address all correspondence and requests for reprints to: Nozomu Nishi, Department of Endocrinology, Faculty of Medicine, Kagawa Medical University, 1750–1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail: nnishi{at}kms.ac.jp
 |
Abstract
|
|---|
The rat prostate is dependent on androgen for normal growth and
differentiation. In addition, the organ undergoes rapid cell death upon
withdrawal of androgen on castration, and the atrophied tissue is
capable of regrowth after androgen replacement in adult animals. In our
search for novel factor(s) that participate in this
androgen-induced proliferation of adult rat prostate cells, we have
generated a complementary DNA (cDNA) library enriched in cDNAs
transiently up-regulated after androgen stimulation in castrated rat
ventral prostate using a PCR-based subtractive hybridization technique.
Sequence analysis of about one hundred clones in the library showed
that approximately 70% of them are identical or closely related to
genes of known function, the remaining ones showing no or very low
similarity to any genes characterized previously. Among the former a
new member of the rat aldo-keto reductase superfamily that is closely
related to aflatoxin, B1 aldehyde reductase has been
identified. The newly identified protein (androgen-inducible aldehyde
reductase, AIAR) and rat aflatoxin B1 aldehyde reductase
(AFAR) exhibit 80% amino acid sequence homology. The enzymatic
activity toward 4-nitrobenzaldehyde of recombinant AIAR expressed
in Escherichia coli was about 16% of that of rat AFAR.
Northern blot analysis revealed AIAR expression in various adult rat
tissues in addition to the ventral and dorsolateral prostates, which
differs from the highly restricted expression of AFAR in the kidney and
liver. The AIAR messenger RNA (mRNA) content of the ventral prostate
was low in normal and castrated rats, transiently increased after
androgen administration to castrated rats, attaining a peak 12–24 h
after the treatment. Although the physiological substrate(s) of AIAR
has not been identified, the current results suggest that AIAR
expression is associated with some growth-related processes in
regrowing rat prostate.
|
Introduction
|
|---|
IT IS NOW generally accepted that
epithelial-stromal interactions play a pivotal role in the growth- and
differentiation-promoting action of androgen in target tissues
including the prostate. These interactions are believed to be regulated
by paracrine signaling molecules produced in an androgen-dependent
manner. Keratinocyte growth factor (KGF), a member of the fibroblast
growth factor (FGF) family (FGF-7), has received attention as a
mediator of stromal to epithelial communication because of its unique
properties: KGF is only secreted by cells of mesenchymal origin and
appears to act specifically on epithelial cells (1, 2). Indeed, the
participation of KGF in morphogenetic epithelial-mesenchymal
interactions in developing mammary gland, salivary gland and lung has
been reported (3, 4). In the case of male accessory glands, KGF also
has been proposed to be a candidate stromal-derived factor responsible
for androgen-dependent growth and differentiation of the seminal
vesicle and prostate (5, 6). However, there is controversy regarding
the presence of androgen response element in the KGF promoter (7, 8)
and androgen regulation of KGF expression in vivo (9, 10, 11).
Recently, Thomson and Cunha showed that FGF-10, another member of the
FGF family, exhibited properties consistent with a mesenchymal
paracrine regulator of epithelial growth in the developing rat prostate
and seminal vesicle (12). The expression of FGF-10, however, was not
regulated by androgens in vivo.
In a previous study, we examined changes in the expression of several
growth factor systems during castration-induced involution and
subsequent androgen-induced regrowth of rat prostates. Our work was
based on the assumption that the expression of one or more specific
growth factor systems that mediate the androgen action is transiently
up-regulated after androgen administration to castrated rats. Contrary
to our expectation, no growth factor system examined, including
epidermal growth factor, transforming growth factor-
, transforming
growth factor-ß1, basic FGF, KGF, and hepatocyte growth factor
showed the "ideal" change during the androgenic manipulation
(9).
The messenger RNA (mRNA) differential display and the PCR-based
subtractive hybridization techniques have been successfully used to
identify differentially expressed genes in a wide variety of tissues.
Novel genes associated with the transformation and castration-induced
apoptosis of prostate cells have been identified by means of these
methods (13, 14, 15, 16). In the present study, we used the latter technique to
find novel factor(s) that may participate in androgen-dependent growth
of prostate cells. Sequence analysis of about one hundred clones in a
cDNA library produced by means of the PCR-based subtractive
hybridization technique, and subsequent Northern blot analysis of
selected clones resulted in the isolation of several novel genes that
show close to the "ideal" change during the androgenic
manipulation. Here, we describe characterization of a new member of the
rat aldo-keto reductase superfamily whose expression is transiently
up-regulated by androgen in regrowing rat prostate.
The aldo-keto reductases comprise a functionally diverse gene family
that catalyzes the NADPH-dependant reduction of a variety of biogenic
and xenobiotic carbonyl compounds, including carcinogens. The newly
identified member of the superfamily androgen-inducible aldehyde
reductase (AIAR) exhibited significant homology to rat and human
aflatoxin B1 aldehyde reductase (AFAR). AFARs metabolize not only
aflatoxin B1, a potent hepatocarcinogen, but also a variety of
aldehydes. AIAR may afford protection to rapidly proliferating prostate
cells against chemical-induced carcinogenesis.
|
Materials and Methods
|
|---|
Animals and hormonal treatment
Testosterone propionate was purchased from Nakarai Chemicals
Ltd. (Kyoto, Japan). Mature (12 weeks, 400–420 g) male Sprague Dawley
rats were obtained from CLEA Japan (Tokyo, Japan). Rats were housed at
20-25 C with 12-h periods of light and darkness. Pelleted food and tap
water were supplied ad libitum. Male rats were castrated by
means of a scrotal incision under ether anesthesia. The castrated rats
were maintained under standard laboratory conditions for 7 days.
Treatment of 7-day castrated rats with exogenous androgen comprised
daily sc injections of testosterone propionate (2 mg/rat) for up to 5
days. At various times following castration and androgen treatment,
groups of rats were killed by cervical dislocation. The ventral
prostate, liver, and kidney were removed and frozen in liquid nitrogen
for later RNA extraction.
Subtractive hybridization and RACE analysis
Total RNA was extracted from rat tissue specimens by the method
of Chomczynski and Sacchi (17). Poly(A)+RNA was
isolated from the total RNA fraction using a PolyATtract mRNA isolation
system (Promega Corp., Madison, WI).
Subtractive hybridization was carried out using a PCR-select cDNA
subtraction kit (CLONTECH Laboratories, Inc., Palo Alto, CA) according to the manufacturer’s protocols. Briefly,
double-strand cDNA was synthesized using 2 µg of
poly(A)+RNA isolated from ventral prostates of
untreated rats (N), 7-day castrated rats (C7), and C7 treated with
androgen for 6 h (C7T0.25), 12 h (C7T0.5), and 24 h
(C7T1). A mixture of equal amounts of cDNA from N and C7 was used as
the "driver", and one of that from C7T0.25, C7T0.5 and C7T1 as the
"tester." After two rounds of PCR-based subtraction, the enriched
cDNAs were cloned into the pGEM-T Easy vector (Promega Corp.) for screening.
For 5'- and 3'-RACE analysis, an adaptor-ligated cDNA library was
generated using a mixture of equal amounts of
poly(A)+RNA from C7T0.25, C7T0.5 and C7T1, and a
Marathon cDNA amplification kit (CLONTECH Laboratories, Inc.). Amplification of 5' and 3' cDNA fragments was performed
by PCR using a specific adaptor primer supplied in the kit and gene
specific primers, 5'-GTAGGTCTCAGACCAGCTATTCCC-3' (5'-RACE) and
5'-CTGCCTCAGATACTTCGGACTGAG-3' (3'-RACE).
Screening of the human prostate cDNA library
The human prostate cDNA library (human prostate 5'-stretch plus
cDNA library, CLONTECH Laboratories, Inc.) was screened
with a cDNA clone obtained by subtractive hybridization. The probe was
labeled with digoxigenin as described below.
Northern blot analysis
One microgram of poly(A)+RNA was
electrophoresed on a 2.2 M formaldehyde-1% agarose gel,
transferred to a nylon membrane (Hybond-N, Amersham Pharmacia Biotech, Uppsala, Sweden), and then cross-linked by UV
irradiation. After prehybridization, the blot was incubated with probes
labeled with digoxigenin for 15 h at 65 C. The membrane was washed
with 2 x SSC/0.1% SDS at room temperature, and then with
0.1 x SSC/0.1% SDS at 65 C. The hybridized probe was detected on
x-ray film as to chemiluminescence using an alkaline
phosphatase-conjugated antidigoxigenin antibody (Roche Molecular Biochemicals, Mannheim, Germany) and Lumi-Phos 530 (Lumigen
Inc., Southfield, MI). The results were normalized as to the content
per cell of each mRNA species as described (9).
The cDNA probe for rat AFAR was obtained by means of PCR using
oligonucleotide primers, 5'-TCCGCTAAGATACATCTGCCTTGG-3', and
5'-TTGGGGCTCAGCCAGCTCTCACTT-3', and first-strand cDNA from rat liver.
All the probes were labeled with digoxigenin-11-dUTP by the method of
Lanzillo (18).
Bacterial expression and isolation of recombinant AIAR and
AFAR
The coding region for AIAR was amplified by PCR from
first-strand cDNA prepared from the poly(A)+ RNA
fraction of rat ventral prostate using forward and reverse primers
tagged with extra 5' EcoRI
(5'-CGTCCTGAATTCCCATGTCCCGGTCTCCGGCACCCCGCGCC-3') and XhoI
(5'-CGACCGCTCGAGCTATCTGAAGTAGTTGGGACACTCGTG-3') sequences,
respectively, and then digested with EcoRI and
XhoI. The coding region for AFAR was amplified by PCR from
first-strand cDNA prepared from the poly(A)+ RNA
fraction of rat liver using forward and reverse primers tagged with
extra 5' EcoRI
(5'-CGTCCTGAATTCCCATGTCGCAAGCCCGGCCTGCCACTGTG-3') and XhoI
(5'-CGACCGCTCGAGTTAGCGGAAATAGTTGGGACACTCGTG-3') sequences,
respectively, and then digested with EcoRI and
XhoI. The digested cDNA fragments were inserted individually
into the EcoRI-XhoI site of pGEX-4T-2
(Amersham Pharmacia Biotech) yielding expression
vectors for fusion proteins between glutathione S-transferase (GST) and
AIAR (pGEX-AIAR) or rat AFAR (pGEX-rAFAR).
Escherichia coli BL21 cells carrying the expression vectors
were grown in 2x YT medium supplemented with 10% (wt/vol) glucose and
100 µg/ml ampicillin to an optical density at 600 nm of 1.0. The
expression of fusion proteins was induced by the addition of 0.1
mM
isopropyl-ß-D-thiogalactopyranoside, and then
the culture was continued for 2 h at 37 C. The cell pellet was
suspended in 10 mM Tris-HCl (pH 7.5) containing
0.5 M NaCl and 1 mM
phenylmethlysulfonyl fluoride, and then the cells were disrupted by
sonication. The sonicate was supplemented with 1% (wt/vol)
3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS)
and stirred for 30 min at 4 C, followed by centrifugation. The
resulting supernatant was subjected to affinity chromatography on a
glutathione-Sepharose column (Amersham Pharmacia Biotech).
The affinity-purified fusion proteins were digested with thrombin and
the released GST moiety was removed with a glutathione-Sepharose
column.
Enzyme assay
Aldehyde reductase activity was determined at 25 C using 0.67
mM 4-nitrobenzaldehyde and 0.2 mM NADPH in 100
mM sodium phosphate buffer (pH 7.0). The reaction was
monitored at 340 nm. Protein concentrations were determined by means of
the bicinchoninic acid (BCA) assay using BSA as a standard.
|
Results
|
|---|
Identification of growth-associated mRNAs in rat prostate by
subtractive hybridization
To carry out PCR-based subtractive hybridization, cDNAs were
prepared from ventral prostate of three different androgenic statuses
in vivo: prostate tissues were obtained from normal rats
(N), 7-day castrated rats (C7) and C7 treated with androgen for 6, 12,
and 24 h (C7T0.25, 0.5, and 1). We constructed a library enriched
in cDNAs transiently up-regulated by androgen in castrated rat prostate
by subtracting cDNAs from (C7T0.25 + C7T0.5 + C7T1) with those from (N
+ C7). Sequence analysis of 108 clones in the library showed that 69
(37 nonredundant clones) were identical or closely related to known
genes, the remaining clones showing no or very low similarity to any
genes characterized previously. No cDNA clone for prostatic binding
protein (PBP), a major androgen-dependent secretory protein of rat
ventral prostate which accounts for more than 30% of the total protein
in the normal tissue, was found.
Based on the sequence data, about 30 clones were selected for analysis
of androgen dependency by Northern blotting. As a result the expression
of several clones was found to be transiently up-regulated in
androgen-stimulated tissues (Fig. 1
and
Table 1). One of the clones, AIEG300,
showed significant homology to rat aflatoxin B1
aldehyde reductase (AFAR) (19, 20), and thus it was subjected to
further characterization in the present study.
View larger version (55K):
[in this window]
[in a new window]
|
Figure 1. Northern blot analysis of gene expression during
castration-induced involution and androgen-induced regrowth of rat
ventral prostate. Poly(A)+RNA was prepared from rat ventral
prostates collected at various times following castration and androgen
treatment. Blots made from poly(A)+RNA (1 µg) were
hybridized to various probes labeled with digoxigenin. N, control rats;
C7, 7-day castrated rats; C7T0.25-C7T5, C7 treated with daily
injections of testosterone propionate for 0.25 days (6 h)-5 days.
AIEG291-AIEG626, cDNA clones obtained by means of a PCR-based cDNA
subtraction technique. PBP (C1), C1 component of prostatic binding
protein.
|
|
The effect of castration on the AIEG300 mRNA content (per cell) was
negligible, but androgen replacement in castrated rats resulted in a
rapid increase in the content of AIEG message (Fig. 2). It increased about 5-fold in over
7-day castrated rats within 12 h after androgen administration and
decreased thereafter to near the control level. On the contrary, the
content of mRNA for the C1 component of PBP decreased to an
undetectable level with castration and recovered steadily after
androgen replacement (Fig. 2).
View larger version (26K):
[in this window]
[in a new window]
|
Figure 2. Changes in mRNA expression per cell of AIEG300 and
the C1 component of PBP during castration-induced involution and
androgen-induced regrowth of rat ventral prostate. The maximum and
control values were taken as 100% in the cases of AIEG300 and PBP
(C1), respectively. A representative analysis from three separate
analyses of three pools of prostates obtained at each time point is
shown.
|
|
The AIEG300 mRNA was expressed at higher levels in the kidney and liver
than in the prostate (see below). Although many genes are known to be
under androgenic control in the kidney and liver, castration and
subsequent androgen replacement had negligible to moderate influence on
AIEG300 mRNA content in these tissues (Table 2).
Determination of the full-length sequence of the cDNA corresponding
to AIEG300 and cloning of the human counterpart
As AIEG300 exhibited homology to the 3'-coding region of rat AFAR,
the full-length sequence of the corresponding cDNA was determined by
means of the 5'- and 3'-RACE methods. The sequence was confirmed by
amplification of the full-length cDNA by PCR and sequence analysis of
the PCR products. This cDNA (termed androgen-inducible aldehyde
reductase, AIAR) comprises 1271 bp with a 1017 bp ORF (Fig. 3). The predicted AIAR protein is eleven
amino acids longer than rat AFAR due to an insertion at N terminus.
AIAR showed the highest homology (about 90% amino acid homology) with
human AFAR (27), whereas AIAR and rat AFAR exhibited 80% homology
(Fig. 4). As expected from the sequence
similarity data, screening of a human prostate cDNA library with
AIEG300 resulted in the isolation of several cDNA clones which
exhibited complete sequence identity with human AFAR (data not
shown).
View larger version (59K):
[in this window]
[in a new window]
|
Figure 3. Nucleotide and deduced amino acid sequences of
androgen-inducible aldehyde reductase (AIAR, full-length sequence of
AIEG300). The original AIEG300 sequence is underlined.
The polyadenylation signal, AATAAA, is double
underlined.
|
|
View larger version (45K):
[in this window]
[in a new window]
|
Figure 4. Multiple sequence alignment of AIAR with rat AFAR
(20 ) and human AFAR (27 ). Dots represent gaps for better
alignment. Dashes represent amino acid residues which
are identical with those of AIAR.
|
|
Tissue distribution of AIAR and rat AFAR transcripts
Northern blot analysis was performed to determine the tissue
distribution of AIAR mRNA and to compare it with that of rat AFAR. cDNA
probes corresponding to the 3' noncoding region, in which there is only
low sequence similarity between AIAR and rat AFAR, were used in this
experiment to avoid cross-hybridization. A single AIAR transcript of
about 1.4 kb was detected in a wide variety of adult rat tissues, with
the highest expression in the kidney (Fig. 5). Although both AIAR and rat AFAR
exhibited the highest degree of expression in the kidney, rat AFAR
exhibited a restricted tissue distribution with detectable transcript
levels present in the kidney and liver under the conditions used (Fig. 5).
View larger version (51K):
[in this window]
[in a new window]
|
Figure 5. Northern blot analysis of AIAR and rat AFAR
(rAFAR) expression. Poly(A)+RNA (1 µg) extracted from
different rat tissues was probed with AIAR or rat AFAR cDNA labeled
with digoxigenin. The blots were stripped and then reprobed with
digoxigenin-labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
cDNA. SG, Submaxillary gland; VP, ventral prostate; DLP, dorsolateral
prostate; SV, seminal vesicle.
|
|
Demonstration of enzymatic activity of recombinant AIAR
To determine whether or not AIAR has reductase activity, AIAR and
rat AFAR were expressed in Escherichia coli as GST-fusion
proteins. The recombinant proteins were efficiently produced as soluble
proteins, and purified to apparent homogeneity by glutathione-affinity
chromatography (Fig. 6). The fusion
proteins were digested with thrombin, and the GST moiety was removed by
affinity chromatography. The apparent molecular weight of the purified
AIAR was slightly lower than the calculated value (37, 601). To
determine the molecular weight accurately, the two proteins were
analyzed by mass spectrometry. Their molecular weights were determined
to be 37,550 (AIAR) and 36,826 (rat AFAR, calculated value =
36,745).
View larger version (61K):
[in this window]
[in a new window]
|
Figure 6. Purification profiles of AIAR and rat AFAR on
SDS-PAGE. Samples at each purification step for AIAR (lanes 2–4) and
rat AFAR (lanes 5–7) were electrophoretically separated in a SDS/12%
polyacrylamide gel under reducing conditions and then stained with
Coomassie brilliant blue R-250. Lane 1, molecular weight markers; lane
2, Escherichia coli BL21/pGEX-AIAR crude extract; lanes
3 and 6, eluate from glutathione-Sepharose; lanes 4 and 7, purified
(GST-tag-free) AIAR and rat AFAR, respectively; lane 5,
Escherichia coli BL21/pGEX-rAFAR crude extract.
|
|
The enzymatic activities of recombinant AIAR and rat AFAR were measured
by using a prototype aldo-keto reductase substrate, 4-nitrobenzaldehyde
(4-NBA). The specific activities of AIAR and rat AFAR were 0.29 and
1.77 µmol/min·mg protein (at 25 C), respectively.
|
Discussion
|
|---|
The subtractive hybridization and RNA differential display
techniques are powerful tools for screening and identifying altered
gene expression in two or more cell/tissue types and during
physiological as well as pathological processes. Many novel genes have
been identified using these techniques including apoptosis- and
transformation-associated genes in the prostate. There is, however, a
general problem associated with these approaches. It is not easy to
determine or even speculate the function of a newly identified gene
unless it exhibits sequence homology with a gene of known function. In
this study, we have identified several novel genes transiently
up-regulated in androgen-stimulated (regrowing) rat prostate using a
PCR-based subtractive hybridization technique. Most of the transiently
up-regulated messages showed sequence similarity with previously
identified genes. Among them, AIEG300 was selected for close
examination in this study based on the extensive homology between
AIEG300 and a detoxification enzyme, rat aflatoxin
B1 aldehyde reductase.
AFAR was first reported by Hayes et al. (19) as an
ethoxyquin (a chemoprotector)-inducible aldehyde reductase in rat liver
implicated in the detoxification of aflatoxin B1
(AFB1). They cloned rat AFAR cDNA and found that
a 140-bp region of a human expressed sequence tag (EST) clone exhibited
85% sequence identity with that portion of rat AFAR (20). Recently,
they reported the molecular cloning of a novel member of the human
aldo-keto reductase superfamily based on the sequence of the EST clone
(27). Rat AFAR and the human enzyme (termed human AFAR) are distantly
related to the aldo-keto reductase family of enzymes, and these two
enzymes appear to constitute a new family, AKR7 (27).
The sequence homology search revealed that AIEG300 (AIAR) exhibited the
highest homology with human AFAR. The presence of extra amino acid
residues at the amino terminus relative to rat AFAR is common to AIAR
and human AFAR. AIAR showed apparent enzyme activity toward 4-NBA, but
it was only about 16% of that of rat AFAR. The reductase activity of
human AFAR toward 4-NBA was also lower than that of rat AFAR (27). In
addition, Northern blot analysis showed that both AIAR and human AFAR
transcripts are widely distributed in rat and human tissues,
respectively, which is in sharp contrast to the highly restricted
expression of rat AFAR. These results suggest that human AFAR is not
the human counterpart of rat AFAR, but one of AIAR identified in the
present study. Also, it is possible that there is a true "human
AFAR," which might be induced by chemoprotectors such as ethoxyquin,
in human liver.
It is generally accepted that drug- and carcinogen-metabolizing
enzymes are involved in the regulation of the local levels of
carcinogens and hence are responsible for the susceptibility to
chemical-induced carcinogenesis. In human prostate, high
interindividual variation in drug-metabolizing enzymes, cytochrome
P-450 2D6 and N-acetyltransferase, has been implicated in differences
in cancer risk (28). Rat and human AFAR have been shown to metabolize a
panel of compounds including AFB1, succinic
semialdehyde (SSA), 2-carboxybenzaldehyde (2-CBA), and 16-oxo-estrone
in vitro (27). Although human AFAR was suggested to function
as both a SSA reductase and a 2-CBA reductase in vivo, its
physiological substrate(s) has not been clearly identified. Currently,
the physiological substrate(s) of AIAR is also unknown. However, it is
highly probable that AIAR can metabolize a wide variety of compounds
including chemical carcinogens because AIAR exhibited extensive
structural similarity with human AFAR. The up-regulation of AIAR
expression during regrowth of rat prostate is favorable in this
context. Cell proliferation/DNA synthesis is an integral part of the
process of conversion of DNA adducts (carcinogen-DNA adducts) to
mutations. Increased activities of drug-metabolizing enzymes may
suppress the formation of DNA adducts, thus leading to lowered risk of
carcinogenesis during active cell proliferation. Among rat tissues
examined, only the ventral and dorsolateral prostates expressed AIAR
mRNA at levels comparable to those in the liver and kidney. As there
have been no reports showing that the prostate expresses
drug-metabolizing enzymes at high levels, it is possible that AIAR
participates in the prostate-specific function, that is, the production
of seminal fluid components. AIAR may afford protection to sperm DNA by
decreasing active chemicals in seminal fluid.
The content of AIAR mRNA (mRNA content per cell) increased after
androgen administration to castrated rats, attaining a peak 12–24 h
after the treatment, and then decreased to the control level. As DNA
synthesis activity in regrowing prostate reaches a peak 3 days after
androgen replacement (9, 29), the validity of the above speculation
must be verified by analyzing AIAR expression at the protein level.
Androgen replacement resulted in about 5-fold induction of AIAR mRNA,
whereas castration caused only a slight decrease in the prostate. On
the other hand, the influence of the androgen manipulation on AIAR mRNA
in the liver and kidney was moderate at most. The expression of
prostatic binding protein (PBP), a major androgen-dependent secretory
protein in rat ventral prostate, decreases to an undetectable level on
castration and returns to the control level 5–7 days after androgen
administration. Several androgen response elements have been identified
in the first intron and 5'-flanking region of the prostatic binding
protein gene (30). Analysis of response elements of the AIAR gene is
needed to clarify the mechanism underlying androgenic regulation of
AIAR expression in the prostate.
|
Footnotes
|
|---|
1 This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science and Culture of Japan.
The nucleotide sequence for AIAR cDNA has been deposited in the
DDBJ/EMBL/GenBank nucleotide sequence databases under the Accession No.
AB037424. 
Received February 9, 2000.
|
References
|
|---|
-
Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA 1989 Human KGF is FGF- related with properties of a paracrine effector
of epithelial cell growth. Science 245:752–755[Abstract/Free Full Text]
-
Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S,
Aaronson SA 1989 Purification and characterization of a newly
identified growth factor specific for epithelial cells. Proc Natl Acad
Sci USA 86:802–806[Abstract/Free Full Text]
-
Mason IJ, Fuller Pace F, Smith R, Dickson C 1994 FGF-7 (keratinocyte growth factor) expression during mouse development
suggests roles in myogenesis, forebrain regionalisation and
epithelial-mesenchymal interactions. Mech Dev 45:15–30[CrossRef][Medline]
-
Finch PW, Cunha GR, Rubin JS, Wong J, Ron D 1995 Pattern of keratinocyte growth factor and keratinocyte growth factor
receptor expression during mouse fetal development suggests a role in
mediating morphogenetic mesenchymal-epithelial interactions. Dev Dyn 203:223–240[Medline]
-
Alarid ET, Rubin JS, Young P, Chedid M, Ron D, Aaronson
SA, Cunha GR 1994 Keratinocyte growth factor functions in
epithelial induction during seminal vesicle development. Proc Natl Acad
Sci USA 91:1074–1078[Abstract/Free Full Text]
-
Sugimura Y, Foster BA, Hom YK, Lipschutz JH, Rubin JS,
Finch PW, Aaronson SA, Hayashi N, Kawamura J, Cunha GR 1996 Keratinocyte growth factor (KGF) can replace testosterone in the ductal
branching morphogenesis of the rat ventral prostate. Int J Dev Biol 40:941–951[Medline]
-
Finch PW, Lengel C, Chedid M 1995 Cloning and
characterization of the promoter region of the human keratinocyte
growth factor gene. J Biol Chem 270:11230–11237[Abstract/Free Full Text]
-
Fasciana C, van der Made AC, Faber PW, Trapman J 1996 Androgen regulation of the rat keratinocyte growth factor
(KGF/FGF7) promoter. Biochem Biophys Res Commun 220:858–863[CrossRef][Medline]
-
Nishi N, Oya H, Matsumoto K, Nakamura T, Miyanaka H,
Wada F 1996 Changes in gene expression of growth factors and their
receptors during castration-induced involution and androgen-induced
regrowth of rat prostates. Prostate 28:139–152[CrossRef][Medline]
-
Nemeth JA, Zelner DJ, Lang S, Lee C 1998 Keratinocyte growth factor in the rat ventral prostate:
androgen-independent expression. J Endocrinol 156:115–125[Abstract]
-
Planz B, Wang Q, Kirley SD, Lin CW, McDougal WS 1998 Androgen responsiveness of stromal cells of the human prostate:
regulation of cell proliferation and keratinocyte growth factor by
androgen. J Urol 160:1850–1855[CrossRef][Medline]
-
Thomson AA, Cunha GR 1999 Prostatic growth and
development are regulated by FGF10. Development 126:3693–3701[Abstract]
-
Wang FL, Wang Y, Wong WK, Liu Y, Addivinola FJ, Liang P,
Chen LB, Kantoff PW, Pardee AB 1996 Two differentially expressed
genes in normal human prostate tissue and in carcinoma. Cancer Res 56:3634–3637[Abstract/Free Full Text]
-
Wang Z, Tufts R, Haleem R, Cai X 1997 Genes
regulated by androgen in the rat ventral prostate. Proc Natl Acad Sci
USA 94:12999–13004[Abstract/Free Full Text]
-
Gubbay J, Doyle JP, Skinner M, Heintz N 1998 Changing patterns of gene expression identify multiple steps during
regression of rat prostate in vivo. Endocrinology 139:2935–2943[Abstract/Free Full Text]
-
Cole KA, Chuaqui RF, Katz K, Pack S, Zhuang Z,
Cole CE, Lyne JC, Linehan WM, Liotta LA, Emmert Buck MR 1998 cDNA
sequencing and analysis of POV1 (PB39): a novel gene up-regulated in
prostate cancer. Genomics 51:282–287[CrossRef][Medline]
-
Chomczynski P, Sacchi N 1987 Single-step method of
RNA isolation by acid guanidinium thiocyanate-phenol-chloroform
extraction. Anal Biochem 162:156–159[Medline]
-
Lanzillo JJ 1991 Chemiluminescent nucleic acid
detection with digoxigenin- labeled probes: a model system with probes
for angiotensin converting enzyme which detect less than one attomole
of target DNA. Anal Biochem 194:45–53[CrossRef][Medline]
-
Hayes JD, Judah DJ, Neal GE 1993 Resistance
to aflatoxin B1 is associated with the expression of a novel aldo-keto
reductase which has catalytic activity towards a cytotoxic
aldehyde-containing metabolite of the toxin. Cancer Res 53:3887–3894[Abstract/Free Full Text]
-
Ellis EM, Judah DJ, Neal GE, Hayes JD 1993 An
ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes
aflatoxin B1 defines a subfamily of aldo-keto reductases. Proc Natl
Acad Sci USA 90:10350–10354[Abstract/Free Full Text]
-
Conway G 1995 A novel gene expressed during
zebrafish gastrulation identified by differential RNA display. Mech Dev 52:383–391[CrossRef][Medline]
-
Grillasca JP, Gastaldi M, Khiri H, Dace A, Peyrol N,
Reynier P, Torresani J, Planells R 1997 Cloning and initial
characterization of human and mouse Spot 14 genes. FEBS Lett 401:38–42[CrossRef][Medline]
-
Ikeda J, Kaneda S, Kuwabara K, Ogawa S, Kobayashi
T, Matsumoto M, Yura T, Yanagi H 1997 Cloning and expression of
cDNA encoding the human 150 kDa oxygen-regulated protein, ORP150.
Biochem Biophys Res Commun 230:94–99[CrossRef][Medline]
-
Levanon D, Hsieh CL, Francke U, Dawson PA, Ridgway
ND, Brown MS, Goldstein JL 1990 cDNA cloning of human
oxysterol-binding protein and localization of the gene to human
chromosome 11 and mouse chromosome 19. Genomics 7:65–74[CrossRef][Medline]
-
Schmalix WA, Bandlow W 1994 SWH1 from yeast encodes
a candidate nuclear factor containing ankyrin repeats and showing
homology to mammalian oxysterol-binding protein. Biochim Biophys Acta 1219:205–210[Medline]
-
Passreiter M, Anton M, Lay D, Frank R, Harter C, Wieland
FT, Gorgas K, Just WW, Huber C, Saffrich R, Anton M, Passreiter M,
Ansorge W, Gorgas K, Just W 1998 Peroxisome biogenesis:
involvement of ARF and coatomer. J Cell Biol 141:373–383[Abstract/Free Full Text]
-
Ireland LS, Harrison DJ, Neal GE, Hayes JD 1998 Molecular cloning, expression and catalytic activity of a human
AKR7 member of the aldo-keto reductase superfamily: evidence that the
major 2-carboxybenzaldehyde reductase from human liver is a homologue
of rat aflatoxin B1-aldehyde reductase. Biochem J 332:21–34
-
Agundez JA, Martinez C, Olivera M, Gallardo L, Ladero
JM, Rosado C, Prados J, Rodriguez Molina J, Resel L, Benitez J 1998 Expression in human prostate of drug- and carcinogen-metabolizing
enzymes: association with prostate cancer risk. Br J Cancer 78:1361–1367[Medline]
-
Sufrin G, Coffey DS 1973 A new model for studying
the effect of drugs on prostatic growth. 1. Antiandrogens and DNA
synthesis. Invest Urol 11:45–54[Medline]
-
Tan JA, Marschke KB, Ho KC, Perry ST, Wilson EM, French
FS, Tan J, Marschke KB, Ho KC, Perry ST, Wilson EM, French FS 1992 Response elements of the androgen-regulated C3 gene. J Biol Chem 267:4456–4466[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
Y. Kashio, K. Nakamura, M. J. Abedin, M. Seki, N. Nishi, N. Yoshida, T. Nakamura, and M. Hirashima
Galectin-9 Induces Apoptosis Through the Calcium-Calpain-Caspase-1 Pathway
J. Immunol.,
April 1, 2003;
170(7):
3631 - 3636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Lane
Diabetic kidney disease: impact of puberty
Am J Physiol Renal Physiol,
October 1, 2002;
283(4):
F589 - F600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kobayashi, T. Kaneko, Y. Iuchi, S. Matsuki, M. Takahashi, I. Sasagawa, T. Nakada, and J. Fujii
Localization and Physiological Implication of Aldose Reductase and Sorbitol Dehydrogenase in Reproductive Tracts and Spermatozoa of Male Rats
J Androl,
September 1, 2002;
23(5):
674 - 683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kozma, E. Brown, E. M. Ellis, and A. J. Lapthorn
The Crystal Structure of Rat Liver AKR7A1. A DIMERIC MEMBER OF THE ALDO-KETO REDUCTASE SUPERFAMILY
J. Biol. Chem.,
May 3, 2002;
277(18):
16285 - 16293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wang, D. W. Rose, O. Hermanson, F. Liu, T. Herman, W. Wu, D. Szeto, A. Gleiberman, A. Krones, K. Pratt, et al.
Regulation of somatic growth by the p160 coactivator p/CIP
PNAS,
November 16, 2000;
(2000)
260463097.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Z. Wang, D. W. Rose, O. Hermanson, F. Liu, T. Herman, W. Wu, D. Szeto, A. Gleiberman, A. Krones, K. Pratt, et al.
Regulation of somatic growth by the p160 coactivator p/CIP
PNAS,
December 5, 2000;
97(25):
13549 - 13554.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
