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Research ArticleArticle

Positive Inter-Regulation between β-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells

Ping Sun, Hui Xiong, Tae Hoon Kim, Bing Ren and Zhuohua Zhang
Molecular Pharmacology February 2006, 69 (2) 520-531; DOI: https://doi.org/10.1124/mol.105.019620
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Tae Hoon Kim
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Bing Ren
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Zhuohua Zhang
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This article has a correction. Please see:

  • Correction to “Positive Inter-Regulation between β-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells” - July 01, 2006

Abstract

Both malignant and normal prostate epithelial cells produce endothelin-1 (ET-1), a critical factor in prostate cancer (CaP) progression. β-Catenin (β-cat), a key component of the Wnt signaling pathway, is also implicated in CaP progression via β-cat/T cell factor (Tcf) signaling. We recently demonstrated that β-cat/Tcf-4 regulates transcription of ET-1 in colon cancer cells. In the present study, we found that Tcf-4 specifically bound to and activated the ET-1 promoter in vivo in human CaP cells and mouse prostate tissue. Expression of ET-1 in DU145 CaP cells was down-regulated by knocking down endogenous β-cat or Tcf-4. Ectopic activation of β-cat/Tcf-4 signaling significantly elevated expression of ET-1 in LNCaP cells. In addition, genetic ablation of β-cat significantly inhibited transcription of ET-1 in primary prostate epithelial cells. Meanwhile, exogenous ET-1 enhanced β-cat/Tcf signaling and ET-1 expression in DU145 cells, which was blocked by both selective phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and endothelin-A receptor antagonist cyclo(l-Leu-d-Trp-d-Asp-l-Pro-d-Val) (BQ123). Furthermore, knockdown of either β-cat or Tcf-4 substantially reduced cell proliferation and potentiated paclitaxel-induced apoptosis in DU145 cells, which largely were rescued by treatment with exogenous ET-1. Together, our results suggest that β-cat/Tcf-4 signaling transcriptionally activates ET-1 in CaP cells; meanwhile, ET-1 enhances β-cat/Tcf-4 signaling and in turn further increases ET-1 expression in a PI3K-dependent manner. The positive inter-regulation between β-cat/Tcf-4 signaling and ET-1 signaling potentiates proliferation and survival of CaP cells, thereby representing a novel mechanism that contributes to CaP progression.

  • Received October 5, 2005.
  • Accepted November 15, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (2)
Molecular Pharmacology
Vol. 69, Issue 2
1 Feb 2006
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Research ArticleArticle

Positive Inter-Regulation between β-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells

Ping Sun, Hui Xiong, Tae Hoon Kim, Bing Ren and Zhuohua Zhang
Molecular Pharmacology February 1, 2006, 69 (2) 520-531; DOI: https://doi.org/10.1124/mol.105.019620

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Research ArticleArticle

Positive Inter-Regulation between β-Catenin/T Cell Factor-4 Signaling and Endothelin-1 Signaling Potentiates Proliferation and Survival of Prostate Cancer Cells

Ping Sun, Hui Xiong, Tae Hoon Kim, Bing Ren and Zhuohua Zhang
Molecular Pharmacology February 1, 2006, 69 (2) 520-531; DOI: https://doi.org/10.1124/mol.105.019620
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