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Lombardi Cancer Center, Georgetown University, Washington, D.C. 20007-2197
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ABSTRACT |
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 Top ABSTRACT IntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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Introduction |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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Most androgen-independent prostate cancers continue to express AR3 after becoming hormone-independent. In fact, one-third of androgen-independent prostate carcinomas show amplification and overexpression of the AR gene, suggesting that maintenance of a functional AR signaling pathway despite castrate levels of testosterone favors cancer cell growth (5) . The notion that the AR may play a role in androgen-independent prostate cancer progression has been strengthened by the discovery of AR mutations in patients with androgen-independent tumors (6 , 7) . Moreover, some of these mutations were shown to alter the binding specificity of receptors for steroid hormones, such that mutant ARs can bind and be activated by estrogens, progesterone, adrenal steroids, and even by androgen antagonists like hydroxyflutamide (8) . Altered ligand specificity can also result from interaction between WT AR and certain AR coactivators (9 , 10) . Potentially, coactivator expression could result in activation of the AR and the progression of prostate cancer despite therapeutic androgen deprivation.
In this report, we describe alteration of AR activation and
steroid hormone specificity by interaction with the oncogene
ß-catenin. ß-Catenin plays a pivotal role in cell-cell adhesion by
linking the cytoplasmic tail of cadherins to 
-catenin and the actin
cytoskeleton. In addition, ß-catenin is a key downstream effector in
the Wnt/Wingless signaling pathway that governs developmental processes
such as cell fate specification, proliferation, polarity, and migration
(11)
. The Wnt pathway has also been implicated in
oncogenesis. The activation of the Wnt/ß-catenin pathway leads to the
formation of a free, signaling pool of ß-catenin that enters the
nucleus and forms a complex with members of the TCF/LEF family of
transcription factors, initiating transcription of new genes
(12)
. In colon cancer, up to 80% of tumors harbor defects
in the APC gene that lead to ß-catenin up-regulation and
constitutive signaling by the ß-catenin-TCF complex
(12)
. Moreover, 50% of colon tumors that express WT APC
have mutations in the ß-catenin gene that up-regulate the levels of
the protein by preventing its degradation (13)
. Recent
studies have shown that ß-catenin is mutated in a variety of human
cancers such as medulloblastoma, hepatocellular carcinoma, endometrial
cancer, and ovarian cancer (12)
. We reported previously
that 5% of primary prostate cancers contained mutations in exon 3 of
the ß-catenin gene, a region that controls the stability of the
protein (14)
. In this report, we show that ß-catenin
enhances androgen-dependent transactivation and that mutant ß-catenin
can relieve the suppression of antiandrogens on androgen-dependent
transcription and change the sensitivity of the AR to ligands. We
suggest that these effects of ß-catenin on AR transcriptional
activity could contribute to prostate cancer progression and that the
role of ß-catenin in oncogenesis may not be limited to its ability to
act as a transcriptional activator in conjunction with the TCF/LEF
proteins.
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Materials and Methods |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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Cell Culture and Transient Transfections.
All cell lines were grown in Improved MEM with 5% fetal bovine
serum. Transient transfection of LNCaP cells was done using the Fugene
reagent (Boehringer Mannheim, Indianapolis, IN) as per the
manufacturer’s instructions. Briefly, LNCaP cells were plated in
Improved MEM without phenol red with 5% CSS at 2 x 105 cells/well in 22-mm wells 3 days before
transfection. At 16–18 h after transfection, cells received fresh
medium containing 5% CSS with or without hormone. The cells were
harvested 36 h after transfection. pRL-CMV Renilla luc
(10 ng) was cotransfected in each sample as an internal control for
transfection efficiency. The luc activities were detected using the
Dual-luc assay (Promega). TSU-Pr1 and CV-1 cells were transfected using
calcium phosphate precipitation. Twenty-four h before transfection,
either 1.25 x 105 TSU-Pr1 cells
or 2 x 105 CV-1 cells were plated
in 35-mm wells. At 16–18 h after transfection, cells were washed three
times in PBS, and new media with 5% CSS with or without hormone were
added. Twenty-four h later, cells were harvested and assayed as
described above. pRL-TK Renilla (10 ng) was cotransfected to
normalize for transfection efficiency. Where indicated, cells were
treated with 10-9
M R1881, a synthetic androgen, or with varying
concentrations of DHT, testosterone, DHEA, androstenedione (all from
Sigma, St. Louis, MO), or bicalutamide [a gift from the Zeneca Corp.
(now AstraZeneca, Wayne, PA)]. All hormones were dissolved in ethanol.
Control cells received a corresponding volume of ethanol only. The
total amount of DNA was kept constant in each transfection by adding
empty pcDNA3.1 vector when appropriate. Cell extracts were assayed for
luc activity at 48 h after transfection. All experiments were
performed in triplicates and repeated at least twice. Results are
expressed as fold transactivation relative to cells transfected with
the reporter gene alone, in the absence of hormone (basal activity),
and are presented as the mean ± SD of triplicate
cultures.
Immunoprecipitation and Immunoblotting.
Whole cell extracts were prepared using a lysis buffer containing
20 mM Tris-HCl (pH 7.8), 140 mM NaCl, 1
mM EDTA, 0.5% NP40, 1 mM phenylmethylsulfonyl
fluoride, and complete protease inhibitors mixture (Boehringer
Mannheim). Where indicated, cells were grown in the presence of
10-8 M DHT for
24 h before protein extraction. Cell lysates were passed several
times through a 30.5-gauge needle to disrupt the nuclei. Protein
extract (500 µg) was incubated with PA1–110 anti-AR antibody for
1 h at 4°C, followed by a 1-h incubation with protein
A/G-Sepharose (Calbiochem, La Jolla, CA). Control immunoprecipitations
were performed using rabbit preimmune serum or a control rabbit
anti-JNK1 antibody (Santa Cruz Biotechnology, Inc.). After four washes
with 0.5 ml of lysis buffer, the pellets were resuspended in
electrophoresis sample buffer, boiled for 5 min, and analyzed on an 8%
Tris-glycine acrylamide gel. Proteins were transferred to a
nitrocellulose membrane and blotted with mouse anti-ß-catenin
antibody. Immunoblotting of the AR was performed with rabbit
anti-AR antibody PA1–110.
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Results |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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. In the absence of androgen, ß-catenin had no effect on
transcription from the MMTV long terminal repeat. Similar results
were obtained using the probasin promoter, indicating that the effect
of ß-catenin on AR function was not specific for a single
androgen-responsive promoter (Fig. 1B)
. Although transient
overexpression of WT ß-catenin also enhanced AR-dependent
transcription, the mutant proteins (S33F and D32Y) had a more
pronounced and consistent effect (Fig. 1B)
. Because it has
been shown previously that the S33F mutant increases the half-life of
the protein and enhances ß-catenin-regulated transcription, the S33F
mutant was chosen for additional experiments.
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The ability of ß-catenin to enhance AR-dependent transcription was
identical with that of the prototypical NRC SRC-1 (Fig. 1C
,
Lanes 6 and 7). The effect of ß-catenin on AR
transactivation was seen across a wide range of androgen concentrations
(Fig. 1D)
.
Because the effect of steroid hormone coactivators on transcription can
depend on the cellular milieu, we studied the interaction between
ß-catenin and AR in several additional cell lines including CV-1
kidney epithelial cells and Cos-7 cells and SKBr-3 human breast
cancer cells. A 2–3-fold induction of AR-dependent transcription was
seen in all cases. Data with CV-1 cells are shown in Fig. 1E
. The effects of ß-catenin on AR transcriptional
activity were specific and did not reflect a general increase in
cellular transcription that may have been induced by ß-catenin. For
example, cotransfection of ß-catenin with another reporter gene
containing a nuclear factor 
B-responsive promoter did not lead to an
increase in the reporter gene expression (Fig. 1F)
.
ß-Catenin Binds to AR.
Given that ß-catenin has several transactivation domains and can act
as a transcriptional activator when bound to TCF (12)
, we
hypothesized that ß-catenin enhanced AR-dependent transcription by
directly interacting with the receptor. We performed
coimmunoprecipitation with lysates from LNCaP cells that constitutively
express high levels of AR and also express ß-catenin. A polyclonal
anti-AR antiserum was used for immunoprecipitation. Rabbit preimmune
serum and a rabbit polyclonal antibody against JNK1 were used as
negative controls to confirm that we did not have nonspecific binding
of ß-catenin to the antiserum. The immune complexes were subjected to
SDS-PAGE/immunoblot analysis using an antibody to ß-catenin.
ß-Catenin was detected in association with anti-AR immune complexes
in the LNCaP cells (Fig. 2
, Lanes 1 and 2), whereas no ß-catenin was
detected in the immune complexes prepared using the control sera
(Lanes 3 and 4). Unlike some SRCs, where binding
to the receptor depends on the presence of hormone, ß-catenin was
coimmunoprecipitated with AR in the absence of hormone. However, the
addition of DHT increased the amount of ß-catenin in the immune
complex.
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, in the TSU-Pr1 cells, ß-catenin increased AR-induced transcription
in response to 1 nM androstenedione to a level comparable
to that of 1 nM testosterone (Fig. 3
A, Lane 7 versus
Lane 3). At 10 nM androstenedione, AR
activity in the presence of ß-catenin increased 9.8-fold over basal
levels, more than twice the activity of AR alone in the presence of 1
nM testosterone (Fig. 3
A, Lane 8 versus
Lane 3). In the absence of ß-catenin, 10
nM androstenedione also increased the
transcriptional activity of AR 2.7-fold over the basal level, probably
because some androstenedione was converted to testosterone and DHT in
TSU-Pr1 cells. In contrast to the response to androstenedione, DHEA at
concentrations from 1–10 nM had no effect on AR
transcriptional activity, irrespective of the presence of ß-catenin
(Fig. 3
A, Lanes 11 and 12 versus
Lanes 9 and 10).
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B, Lane 7 versus Lane 2). We further studied the effect of
ß-catenin on the AR response to the AR antagonist bicalutamide, a
drug commonly used in the treatment of prostate cancer. TSU-Pr1 cells
were transfected with the MMTV-luc reporter, the AR expression plasmid,
and either the mutant ß-catenin plasmid or the empty vector in the
presence of 0.1 nM R1881 and increasing
concentrations of bicalutamide. As shown in Fig. 4
, at each concentration of bicalutamide, the inhibitory effect of the
antiandrogen was diminished by the mutant ß-catenin.
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Discussion |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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AR, like other members of the steroid receptor superfamily, functions as a ligand-activated transcription factor, controlling the expression of genes involved in functions such as cell proliferation, cell growth, differentiation, and cell death. A major challenge has been to define the molecular properties of each hormone receptor that determine its ability to regulate the transcription of specific target genes. Studies within the past few years have lead to the identification of a multitude of cofactors that mediate the transcriptional effects of hormone receptors either as activators or repressors (18) . Most coactivators have been shown to possess intrinsic activation domains that enhance nuclear receptor activity. Some coactivators are parts of complexes containing histone acetyltransferase activity that modulates chromatin structure, thereby influencing the accessibility of transcription factors to the chromatin template (18) .
A large number of proteins that interact directly with steroid hormone
receptors and modulate their activity have been identified recently.
Many of the coactivators have a common site of interaction with the
steroid hormone receptors and modulate transcriptional activity of
nuclear receptors in a ligand-dependent manner. The SRC/NRC subclass
represents the prototype of NRCs (18)
. All three members
of this subclass contain two major transactivation domains and three
highly conserved motifs that mediate the binding of these coactivators
to nuclear receptors. These motifs contain a consensus amino acid
sequence, the LXXLL motif (where L is leucine and
X is any amino acid), called the NR box that binds to
the COOH-terminal end of nuclear receptors (18)
.
ß-Catenin contains five LXXLL motifs, all situated in a
highly conserved central region of the protein containing the
armadillo repeats (19)
. The 12 armadillo repeats form a
single structural unit that provides the interaction sites with APC,
E-cadherin, and TCF/LEF (12)
. This region was previously
shown to adopt an -helical conformation, which is a prerequisite for
nuclear receptor binding (19)
. Whether any of these
regions are responsible for the interaction between ß-catenin and AR
is currently being investigated.
Mutations in AR have been shown previously to change the receptor sensitivity to steroid hormones or antiandrogens such that the mutant ARs are activated by ligands other than androgens and even by antiandrogens. Certain receptor coactivators can change ligand specificity even with WT AR. We show here that ß-catenin increased the transcriptional activity of WT AR not only in the presence of DHT and testosterone but also with ligands such as androstenedione and 17ß-estradiol. In fact, the coactivators ARA70 and ARA55 and now ß-catenin are the only proteins that can activate AR in the presence of 17ß-estradiol. The cornerstone of the treatment of disseminated prostate cancer is the elimination of the testicular androgens either by orchiectomy or by treatment with luteinizing hormone-releasing hormone agonists. However, the adrenal glands continue to supply adrenal androgens like DHEA and androstenedione, which in the prostate are further transformed into more potent androgens that could stimulate the cancer growth. In fact, although the serum testosterone levels are reduced by 90–95% after castration, the intraprostatic concentration of the potent androgen DHT is decreased by only 50–60%, and the serum concentrations of the primary metabolites of DHT are also reduced by only 50–60% (20) . This indicates that the adrenal supply of androgens is significant and could account for as much as 40–50% of the total DHT in the prostate (20) . For this reason, antiandrogens are used in the treatment of disseminated prostate cancer to complement the luteinizing hormone-releasing hormone agonists. In this report, we show that the weak adrenal androgen androstenedione was able to activate AR transcription in the presence of ß-catenin to a level comparable to the potent ligand, DHT. In addition, ß-catenin was able to relieve the inhibition of the antiandrogen bicalutamide on AR-dependent transcription, suggesting that the inhibitory effects of these drugs can be modulated by ß-catenin. These findings add to the previous data suggesting that the interaction between ligand-receptor complexes and cofactors could be essential for steroid receptor function and sensitivity.
Although a number of AR coactivators have been described recently, very little is known about the role of these proteins in disease pathogenesis. Mutations in the oncogene ß-catenin have now been described in numerous cancers, some of which are hormone responsive such as endometrial and prostate cancer. ß-Catenin has also been shown to influence the transcriptional activity of the retinoic acid receptor, indicating that ß-catenin could function as a coactivator for a variety of steroid hormone receptors (21) . We have previously shown that ß-catenin mutations occur focally in prostate cancer, suggesting that these mutations are late events in prostate tumorigenesis and could be related to the development of hormone independence. In conclusion, in hormone-dependent cancers, mutations in ß-catenin may contribute to disease progression by modulating receptor-dependent signaling.
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Note Added in Proof |
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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1 Supported in part by NIH Grants CA57178 and
CA87855 (to E. P. G.). C. I. T. is a recipient of a Young
Investigator Award from the American Society of Clinical Oncology. 
2 To whom requests for reprints should be
addressed, at Lombardi Cancer Center, Georgetown University, 3800
Reservoir Road, NW, Washington, D.C. 20007-2197. Phone:
(202) 687-2207; Fax: (202) 784-1229; E-mail: Gelmanne{at}gunet.georgetown.edu
3 The abbreviations used are: AR, androgen
receptor; TCF, T cell factor; LEF, lymphocyte enhancer factor; MMTV,
mouse mammary tumor virus; luc, luciferase; DHT,
5-dihydrotestosterone; DHEA, dehydroepiandrosterone; CSS,
charcoal-stripped serum; SRC, steroid receptor coactivator; NRC,
nuclear receptor coactivator; WT, wild-type.
Received 3/16/00. Accepted 7/18/00.
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TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionNote Added in ProofREFERENCES |
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C. Labalette, C.-A. Renard, C. Neuveut, M.-A. Buendia, and Y. Wei Interaction and Functional Cooperation between the LIM Protein FHL2, CBP/p300, and {beta}-Catenin Mol. Cell. Biol., December 15, 2004; 24(24): 10689 - 10702. [Abstract] [Full Text] [PDF]
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M. Verras, J. Brown, X. Li, R. Nusse, and Z. Sun Wnt3a Growth Factor Induces Androgen Receptor-Mediated Transcription and Enhances Cell Growth in Human Prostate Cancer Cells Cancer Res., December 15, 2004; 64(24): 8860 - 8866. [Abstract] [Full Text] [PDF]
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H. Zhu, M. Mazor, Y. Kawano, M. M. Walker, H. Y. Leung, K. Armstrong, J. Waxman, and R. M. Kypta Analysis of Wnt Gene Expression in Prostate Cancer: Mutual Inhibition by WNT11 and the Androgen Receptor Cancer Res., November 1, 2004; 64(21): 7918 - 7926. [Abstract] [Full Text] [PDF]
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J. Liu and S. R. Farmer Regulating the Balance between Peroxisome Proliferator-activated Receptor {gamma} and {beta}-Catenin Signaling during Adipogenesis: A GLYCOGEN SYNTHASE KINASE 3{beta} PHOSPHORYLATION-DEFECTIVE MUTANT OF {beta}-CATENIN INHIBITS EXPRESSION OF A SUBSET OF ADIPOGENIC GENES J. Biol. Chem., October 22, 2004; 279(43): 45020 - 45027. [Abstract] [Full Text] [PDF]
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D. Masiello, S.-Y. Chen, Y. Xu, M. C. Verhoeven, E. Choi, A. N. Hollenberg, and S. P. Balk Recruitment of {beta}-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells Mol. Endocrinol., October 1, 2004; 18(10): 2388 - 2401. [Abstract] [Full Text] [PDF]
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J. Hulit, C. Wang, Z. Li, C. Albanese, M. Rao, D. Di Vizio, S. Shah, S. W. Byers, R. Mahmood, L. H. Augenlicht, et al. Cyclin D1 Genetic Heterozygosity Regulates Colonic Epithelial Cell Differentiation and Tumor Number in ApcMin Mice Mol. Cell. Biol., September 1, 2004; 24(17): 7598 - 7611. [Abstract] [Full Text] [PDF]
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Y.-C. Hu, S. Yeh, S.-D. Yeh, E. R. Sampson, J. Huang, P. Li, C.-L. Hsu, H.-J. Ting, H.-K. Lin, L. Wang, et al. Functional Domain and Motif Analyses of Androgen Receptor Coregulator ARA70 and Its Differential Expression in Prostate Cancer J. Biol. Chem., August 6, 2004; 279(32): 33438 - 33446. [Abstract] [Full Text] [PDF]
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L. Wang, H.-K. Lin, Y.-C. Hu, S. Xie, L. Yang, and C. Chang Suppression of Androgen Receptor-mediated Transactivation and Cell Growth by the Glycogen Synthase Kinase 3{beta} in Prostate Cells J. Biol. Chem., July 30, 2004; 279(31): 32444 - 32452. [Abstract] [Full Text] [PDF]
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X. Liao, J. B. Thrasher, J. Holzbeierlein, S. Stanley, and B. Li Glycogen Synthase Kinase-3{beta} Activity Is Required for Androgen-Stimulated Gene Expression in Prostate Cancer Endocrinology, June 1, 2004; 145(6): 2941 - 2949. [Abstract] [Full Text] [PDF]
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L. Levy, Y. Wei, C. Labalette, Y. Wu, C.-A. Renard, M. A. Buendia, and C. Neuveut Acetylation of {beta}-Catenin by p300 Regulates {beta}-Catenin-Tcf4 Interaction Mol. Cell. Biol., April 15, 2004; 24(8): 3404 - 3414. [Abstract] [Full Text] [PDF]
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C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]
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D. R. Chesire, T. A. Dunn, C. M. Ewing, J. Luo, and W. B. Isaacs Identification of Aryl Hydrocarbon Receptor as a Putative Wnt/{beta}-Catenin Pathway Target Gene in Prostate Cancer Cells Cancer Res., April 1, 2004; 64(7): 2523 - 2533. [Abstract] [Full Text] [PDF]
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 M. Rahman, H. Miyamoto, and C. Chang Androgen Receptor Coregulators in Prostate Cancer: Mechanisms and Clinical Implications Clin. Cancer Res., April 1, 2004; 10(7): 2208 - 2219. [Full Text] [PDF]
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Y.-H. Lee, H. D. Campbell, and M. R. Stallcup Developmentally Essential Protein Flightless I Is a Nuclear Receptor Coactivator with Actin Binding Activity Mol. Cell. Biol., March 1, 2004; 24(5): 2103 - 2117. [Abstract] [Full Text] [PDF]
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H. Li, J. H. Kim, S. S. Koh, and M. R. Stallcup Synergistic Effects of Coactivators GRIP1 and {beta}-Catenin on Gene Activation: CROSS-TALK BETWEEN ANDROGEN RECEPTOR AND Wnt SIGNALING PATHWAYS J. Biol. Chem., February 6, 2004; 279(6): 4212 - 4220. [Abstract] [Full Text] [PDF]
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M. J. Linja, K. P. Porkka, Z. Kang, K. J. Savinainen, O. A. Janne, T. L. J. Tammela, R. L. Vessella, J. J. Palvimo, and T. Visakorpi Expression of Androgen Receptor Coregulators in Prostate Cancer Clin. Cancer Res., February 1, 2004; 10(3): 1032 - 1040. [Abstract] [Full Text] [PDF]
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L. G. Horvath, S. M. Henshall, J. G. Kench, D. N. Saunders, C.-S. Lee, D. Golovsky, P. C. Brenner, G. F. O'Neill, R. Kooner, P. D. Stricker, et al. Membranous Expression of Secreted Frizzled-Related Protein 4 Predicts for Good Prognosis in Localized Prostate Cancer and Inhibits PC3 Cellular Proliferation in Vitro Clin. Cancer Res., January 15, 2004; 10(2): 615 - 625. [Abstract] [Full Text] [PDF]
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S. Shah, A. Hecht, R. Pestell, and S. W. Byers Trans-repression of {beta}-Catenin Activity by Nuclear Receptors J. Biol. Chem., November 28, 2003; 278(48): 48137 - 48145. [Abstract] [Full Text] [PDF]
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T. Ohira, R. M. Gemmill, K. Ferguson, S. Kusy, J. Roche, E. Brambilla, C. Zeng, A. Baron, L. Bemis, P. Erickson, et al. WNT7a induces E-cadherin in lung cancer cells PNAS, September 2, 2003; 100(18): 10429 - 10434. [Abstract] [Full Text] [PDF]
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A. L. Amir, M. Barua, N. C. McKnight, S. Cheng, X. Yuan, and S. P. Balk A Direct {beta}-Catenin-independent Interaction between Androgen Receptor and T Cell Factor 4 J. Biol. Chem., August 15, 2003; 278(33): 30828 - 30834. [Abstract] [Full Text] [PDF]
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 W.A. Schulz, M. Burchardt, and M.V. Cronauer Molecular biology of prostate cancer Mol. Hum. Reprod., August 1, 2003; 9(8): 437 - 448. [Abstract] [Full Text] [PDF]
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M. M. Rahman, H. Miyamoto, H. Takatera, S. Yeh, S. Altuwaijri, and C. Chang Reducing the Agonist Activity of Antiandrogens by a Dominant-negative Androgen Receptor Coregulator ARA70 in Prostate Cancer Cells J. Biol. Chem., May 23, 2003; 278(22): 19619 - 19626. [Abstract] [Full Text] [PDF]
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C. J. Loy, K. S. Sim, and E. L. Yong Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions PNAS, April 15, 2003; 100(8): 4562 - 4567. [Abstract] [Full Text] [PDF]
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A. Umar, T. M. Luider, C. A. Berrevoets, J. A. Grootegoed, and A. O. Brinkmann Proteomic Analysis of Androgen-Regulated Protein Expression in a Mouse Fetal Vas Deferens Cell Line Endocrinology, April 1, 2003; 144(4): 1147 - 1154. [Abstract] [Full Text] [PDF]
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H. Mizusaki, K. Kawabe, T. Mukai, E. Ariyoshi, M. Kasahara, H. Yoshioka, A. Swain, and K.-i. Morohashi Dax-1 (Dosage-Sensitive Sex Reversal-Adrenal Hypoplasia Congenita Critical Region on the X Chromosome, Gene 1) Gene Transcription Is Regulated by Wnt4 in the Female Developing Gonad Mol. Endocrinol., April 1, 2003; 17(4): 507 - 519. [Abstract] [Full Text] [PDF]
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L.-N. Song, R. Herrell, S. Byers, S. Shah, E. M. Wilson, and E. P. Gelmann {beta}-Catenin Binds to the Activation Function 2 Region of the Androgen Receptor and Modulates the Effects of the N-Terminal Domain and TIF2 on Ligand-Dependent Transcription Mol. Cell. Biol., March 1, 2003; 23(5): 1674 - 1687. [Abstract] [Full Text] [PDF]
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Y. Wei, C.-A. Renard, C. Labalette, Y. Wu, L. Levy, C. Neuveut, X. Prieur, M. Flajolet, S. Prigent, and M.-A. Buendia Identification of the LIM Protein FHL2 as a Coactivator of beta -Catenin J. Biol. Chem., February 7, 2003; 278(7): 5188 - 5194. [Abstract] [Full Text] [PDF]
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 B. Comuzzi, L. Lambrinidis, H. Rogatsch, S. Godoy-Tundidor, N. Knezevic, I. Krhen, Z. Marekovic, G. Bartsch, H. Klocker, A. Hobisch, et al. The Transcriptional Co-Activator cAMP Response Element-Binding Protein-Binding Protein Is Expressed in Prostate Cancer and Enhances Androgen- and Anti-Androgen-Induced Androgen Receptor Function Am. J. Pathol., January 1, 2003; 162(1): 233 - 241. [Abstract] [Full Text] [PDF]
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M. A. Rao, H. Cheng, A. N. Quayle, H. Nishitani, C. C. Nelson, and P. S. Rennie RanBPM, a Nuclear Protein That Interacts with and Regulates Transcriptional Activity of Androgen Receptor and Glucocorticoid Receptor J. Biol. Chem., December 6, 2002; 277(50): 48020 - 48027. [Abstract] [Full Text] [PDF]
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T. H. Thin, E. Kim, S. Yeh, E. R. Sampson, Y.-T. Chen, L. L. Collins, R. Basavappa, and C. Chang Mutations in the Helix 3 Region of the Androgen Receptor Abrogate ARA70 Promotion of 17beta -Estradiol-induced Androgen Receptor Transactivation J. Biol. Chem., September 20, 2002; 277(39): 36499 - 36508. [Abstract] [Full Text] [PDF]
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M. Sharma, W. W. Chuang, and Z. Sun Phosphatidylinositol 3-Kinase/Akt Stimulates Androgen Pathway through GSK3beta Inhibition and Nuclear beta -Catenin Accumulation J. Biol. Chem., August 16, 2002; 277(34): 30935 - 30941. [Abstract] [Full Text] [PDF]
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S. S. Koh, H. Li, Y.-H. Lee, R. B. Widelitz, C.-M. Chuong, and M. R. Stallcup Synergistic Coactivator Function by Coactivator-associated Arginine Methyltransferase (CARM) 1 and beta -Catenin with Two Different Classes of DNA-binding Transcriptional Activators J. Biol. Chem., July 12, 2002; 277(29): 26031 - 26035. [Abstract] [Full Text] [PDF]
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S. Shah, M. J. Pishvaian, V. Easwaran, P. H. Brown, and S. W. Byers The Role of Cadherin, beta -Catenin, and AP-1 in Retinoid-regulated Carcinoma Cell Differentiation and Proliferation J. Biol. Chem., July 5, 2002; 277(28): 25313 - 25322. [Abstract] [Full Text] [PDF]
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J. E. Pawlowski, J. R. Ertel, M. P. Allen, M. Xu, C. Butler, E. M. Wilson, and M. E. Wierman Liganded Androgen Receptor Interaction with beta -Catenin. NUCLEAR CO-LOCALIZATION AND MODULATION OF TRANSCRIPTIONAL ACTIVITY IN NEURONAL CELLS J. Biol. Chem., May 31, 2002; 277(23): 20702 - 20710. [Abstract] [Full Text] [PDF]
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C. A. Heinlein and C. Chang Androgen Receptor (AR) Coregulators: An Overview Endocr. Rev., April 1, 2002; 23(2): 175 - 200. [Abstract] [Full Text] [PDF]
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F. Yang, X. Li, M. Sharma, C. Y. Sasaki, D. L. Longo, B. Lim, and Z. Sun Linking beta -Catenin to Androgen-signaling Pathway J. Biol. Chem., March 22, 2002; 277(13): 11336 - 11344. [Abstract] [Full Text] [PDF]
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 M. E. Grossmann, H. Huang, and D. J. Tindall Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer J Natl Cancer Inst, November 21, 2001; 93(22): 1687 - 1697. [Abstract] [Full Text] [PDF]
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M. Stanbrough, I. Leav, P. W. L. Kwan, G. J. Bubley, and S. P. Balk Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium PNAS, September 4, 2001; (2001) 191235898. [Abstract] [Full Text] [PDF]
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K. Kimura, M. Markowski, C. Bowen, and E. P. Gelmann Androgen Blocks Apoptosis of Hormone-dependent Prostate Cancer Cells Cancer Res., July 1, 2001; 61(14): 5611 - 5618. [Abstract] [Full Text] [PDF]
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X. Wang, S. Yeh, G. Wu, C.-L. Hsu, L. Wang, T. Chiang, Y. Yang, Y. Guo, and C. Chang Identification and Characterization of a Novel Androgen Receptor Coregulator ARA267-alpha in Prostate Cancer Cells J. Biol. Chem., October 26, 2001; 276(44): 40417 - 40423. [Abstract] [Full Text] [PDF]
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M. Stanbrough, I. Leav, P. W. L. Kwan, G. J. Bubley, and S. P. Balk Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium PNAS, September 11, 2001; 98(19): 10823 - 10828. [Abstract] [Full Text] [PDF]
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