MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on November 16, 2005; DOI: 10.1124/mol.105.019620

This Article
Right arrow Full Text (PDF)
Right arrow Erratum
Right arrow All Versions of this Article:
mol.105.019620v1
69/2/520    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, P.
Right arrow Articles by Zhang, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, P.
Right arrow Articles by Zhang, Z.


Received for publication October 6, 2005.
Revised November 6, 2005.
Accepted for publication November 15, 2005.

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

Ping Sun 1, Hui Xiong 1, Tae-Hoon Kim 2, Bing Ren 2, Zhuohua Zhang 1*

1 Burnham Institute for Medical Research 2 Department of Cellular and Molecular Medicine, UCSD School of Medicine

* Address correspondence to: E-mail: benzz{at}burnham.org

Abstract

Both malignant and normal prostate epithelial cells produce endothelin-1 (ET-1), a critical factor in prostate cancer (CaP) progression. {beta}-Catenin ({beta}-cat), a key component of the Wnt signaling pathway, is also implicated in CaP progression via {beta}-cat/T cell factor (Tcf) signaling. We recently demonstrated that {beta}-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 {beta}-cat or Tcf-4. Ectopic activation of {beta}-cat/Tcf-4 signaling significantly elevated expression of ET-1 in LNCaP cells. In addition, genetic ablation of {beta}-cat significantly inhibited transcription of ET-1 in primary prostate epithelial cells. Meanwhile, exogenous ET-1 enhanced {beta}-cat/Tcf signaling and ET-1 expression in DU145 cells, which was blocked by both selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and endothelin-A receptor antagonist BQ123. Furthermore, knockdown of either {beta}-cat or Tcf-4 substantially reduced cell proliferation and potentiated paclitaxel-induced apoptosis in DU145 cells, which to a great extent were rescued by treatment with exogenous ET-1. Together, our results suggest that {beta}-cat/Tcf-4 signaling transcriptionally activates ET-1 in CaP cells; meanwhile, ET-1 enhances {beta}-cat/Tcf-4 signaling and in turn further increases ET-1 expression in a PI3K-dependent manner. The positive inter-regulation between {beta}-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.


Key words: DNA binding sites, Promoter analysis, Regulation - transcriptional, Mechanisms of cell killing/apoptosis, Oncogenes, Transcription targets


This article has been cited by other articles:


Home page
 Diabetes CareHome page
A. R. Folsom, J. S. Pankow, J. M. Peacock, S. J. Bielinski, G. Heiss, and E. Boerwinkle
Variation in TCF7L2 and Increased Risk of Colon Cancer: The Atherosclerosis Risk in Communities (ARIC) Study
Diabetes Care, May 1, 2008; 31(5): 905 - 909.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics