Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway

S. Liu, R. L. Vinall, C. Tepper, X. B. Shi, L. R. Xue, A. H. Ma, L. Y. Wang, L. D. Fitzgerald, Z. Wu, R. Gandour-Edwards, R. W. DeVere White, H. J. Kung

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We have previously demonstrated that human H2-relaxin can mediate androgen-independent growth of LNCaP through a mechanism that involves the activation of the androgen receptor (AR) signaling pathway. The goal of the current study is to elucidate the mechanism(s) by which H2-relaxin causes activation of the AR pathway. Our data indicate that there is cross-talk between AR and components of the Wnt signaling pathway. Addition of H2-relaxin to LNCaP cells resulted in increased phosphorylation of protein kinase B (Akt) and inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β) with subsequent cytoplasmic accumulation of β-catenin. Immunoprecipitation and immunocytochemical studies demonstrated that the stabilized β-catenin formed a complex with AR, which was then translocated into the nucleus. Chromatin immunoprecipitation analysis determined that the AR/β-catenin complex binds to the proximal region of the prostate-specific antigen promoter. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, using LY294002, prevented both H2-relaxin-mediated phosphorylation of Akt and GSK-3β and translocation of β-catenin/AR into the nucleus. Knockdown of β-catenin levels using a β-catenin-specific small interfering RNA inhibited H2-relaxin-induced AR activity. The combined data demonstrate that PI3K/Akt and components of the Wnt pathway can facilitate H2-relaxin-mediated activation of the AR pathway.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalOncogene
Volume27
Issue number4
DOIs
Publication statusPublished - Jan 17 2008
Externally publishedYes

Fingerprint

Relaxin
Catenins
Androgen Receptors
Phosphatidylinositol 3-Kinase
Glycogen Synthase Kinase 3
Wnt Signaling Pathway
Phosphorylation
Proto-Oncogene Proteins c-akt
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Chromatin Immunoprecipitation
Prostate-Specific Antigen
Immunoprecipitation
Small Interfering RNA
Androgens

Keywords

  • β-catenin
  • Androgen receptor
  • GPCR
  • H2-relaxin
  • Prostate cancer
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Liu, S., Vinall, R. L., Tepper, C., Shi, X. B., Xue, L. R., Ma, A. H., ... Kung, H. J. (2008). Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway. Oncogene, 27(4), 499-505. https://doi.org/10.1038/sj.onc.1210671

Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway. / Liu, S.; Vinall, R. L.; Tepper, C.; Shi, X. B.; Xue, L. R.; Ma, A. H.; Wang, L. Y.; Fitzgerald, L. D.; Wu, Z.; Gandour-Edwards, R.; DeVere White, R. W.; Kung, H. J.

In: Oncogene, Vol. 27, No. 4, 17.01.2008, p. 499-505.

Research output: Contribution to journalArticle

Liu, S, Vinall, RL, Tepper, C, Shi, XB, Xue, LR, Ma, AH, Wang, LY, Fitzgerald, LD, Wu, Z, Gandour-Edwards, R, DeVere White, RW & Kung, HJ 2008, 'Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway', Oncogene, vol. 27, no. 4, pp. 499-505. https://doi.org/10.1038/sj.onc.1210671
Liu S, Vinall RL, Tepper C, Shi XB, Xue LR, Ma AH et al. Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway. Oncogene. 2008 Jan 17;27(4):499-505. https://doi.org/10.1038/sj.onc.1210671
Liu, S. ; Vinall, R. L. ; Tepper, C. ; Shi, X. B. ; Xue, L. R. ; Ma, A. H. ; Wang, L. Y. ; Fitzgerald, L. D. ; Wu, Z. ; Gandour-Edwards, R. ; DeVere White, R. W. ; Kung, H. J. / Inappropriate activation of androgen receptor by relaxin via Β-catenin pathway. In: Oncogene. 2008 ; Vol. 27, No. 4. pp. 499-505.
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