The DOI matches its Crossref record; 92 of the 93 references it cites were found in a registry or an index.
Ligand-dependent inhibition of β-catenin/TCF signaling by androgen receptor
Abstract
Beta-catenin signaling may contribute to prostate cancer (CaP) progression. Although beta-catenin is known to upregulate T cell factor (TCF) target gene expression in CaP cells, recent evidence demonstrates its capacity to enhance ligand-dependent androgen receptor (AR) function. Thus, we wished to further understand the interaction between these two pathways. We find in both CaP cells (CWR22-Rv1, LAPC-4, DU145) and non-CaP cells (HEK-293, TSU, SW480, HCT-116) that beta-catenin/TCF-related transcription (CRT), as measured by activation of a synthetic promoter and that of cyclin D1, is inhibited by androgen treatment. This inhibition is AR-dependent, as it only occurs in cells expressing AR endogenously or transiently, and is abrogated by AR antagonists. Additional analyses convey that the ligand-dependent nature of CRT suppression depends on transactivation-competent AR in the nucleus, but not on indirect effects stemming from AR target gene expression. Given the recent work identifying an AR/beta-catenin interaction, and from our finding that liganded AR does not prompt gross changes in the constitutive nuclear localization of TCF4 or mutant beta-catenin, we hypothesized that transcription factor (i.e. AR and TCF) competition for beta-catenin recruitment may explain, in part, androgen-induced suppression of CRT. To address this idea, we expressed an AR mutant lacking its DNA-binding domain (DBD). This receptor could not orchestrate ligand-dependent CRT repression, thereby providing support for those recent data implicating the AR DBD/LBD as necessary for beta-catenin interaction. Further supporting this hypothesis, TCF/LEF over-expression counteracts androgen-induced suppression of CRT, and requires beta-catenin binding activity to do so. Interestingly, TCF4 over-expression potently antagonizes AR function; however, this inhibition may occur independently of beta-catenin/TCF4 interaction. These results from TCF4 over-expression analyses, taken together, provide further evidence that AR-mediated suppression of CRT is a consequence of limiting amounts of beta-catenin, and not AR target gene expression. Our analyses point to a reciprocal balance between AR and CRT function that may shape critical processes during normal prostate development and tumor progression.
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“Since AR competes with TCF4 for β-catenin binding [21], the presence of FKBP52 may be enough to shift β-catenin to favor AR over TCF4.”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [21]
In the citing paper
“Indeed, ligand-bound AR decreases the transcriptional activity of TCF4 in prostate cancer, colon cancer [21], and neurons [16].”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [21]
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Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684
Identification of c- MYC as a Target of the APC Pathway
He, T.-C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., & Kinzler, K. W. (1998) · Science · doi:10.1126/science.281.5382.1509 · Cited by 4,566
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Morin, P. J., Sparks, A. B., Kořínek, V., Barker, N., Clevers, H. C., Vogelstein, B., & Kinzler, K. W. (1997) · Science · doi:10.1126/science.275.5307.1787 · Cited by 4,000
β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
Tetsu, O., & McCormick, F. (1999) · Nature · doi:10.1038/18884 · Cited by 3,601
Cadherin Cell Adhesion Receptors as a Morphogenetic Regulator
Takeichi, M. (1991) · Science · doi:10.1126/science.2006419 · Cited by 3,283
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., & Clevers, H. (1997) · Science · doi:10.1126/science.275.5307.1784 · Cited by 2,905
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683
Cofactor Dynamics and Sufficiency in Estrogen Receptor–Regulated Transcription
Shang, Y., Hu, X., DiRenzo, J., Lazar, M. A., & Brown, M. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00188-4 · Cited by 1,647
β-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin
Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G., & Birchmeier, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00336-1 · Cited by 1,352
Research works printed but not linked: 2
- Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence MJ, Holcombe RF, Waterman ML . 2001 Nat. Genet. 28: 53–57 · DOI
- Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA . 2000 Cancer Res. 60: 5946–5949
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Androgenetic alopecia: a review
Lolli, F., Pallotti, F., Rossi, A., Fortuna, M. C., Caro, G., Lenzi, A., Sansone, A., & Lombardo, F. P. (2017) · Endocrine · doi:10.1007/s12020-017-1280-y · Cited by 582
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Metadata
- Authors
- Chesire, D. R., & Isaacs, W. B.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Isaacs, William B
- ORCID
- Isaacs, William B
- Venue
- Oncogene
- Published
- 2002-12-04
- Volume
- 21
- Issue
- 55
- Pages
- 8453-8469
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1970833195
- Cited by
- 151
- References
- 93
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 9 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 9 · 2012: 10
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA58236, P50CA058236)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- androgen receptor, β-catenin, TCF/LEF, Wnt signaling, prostate cancer, ligand-dependent transcription, transcription factor competition, TCF4, cyclin D1, DNA-binding domain, transcriptional repression
- MeSH terms
- Animals, Cell Line, Cell Nucleus, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Ligands, Male, Prostatic Neoplasms, Receptors, Androgen, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Signal Transduction, Trans-Activators, beta Catenin, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
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