MolPharm

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


     

Molecular Pharmacology Fast Forward
First published on April 12, 2007; DOI: 10.1124/mol.107.033894

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.107.033894v1
72/1/73    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 Xie, Y.
Right arrow Articles by Tu, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xie, Y.
Right arrow Articles by Tu, Y.


Received for publication January 5, 2007.
Revised April 12, 2007.
Accepted for publication April 12, 2007.

Vasoactive intestinal peptide transactivates the androgen receptor through a PKA-dependent extracellular signal-regulated kinase pathway in prostate cancer LNCaP cells

Yan Xie 1, Dennis W Wolff 1, Ming-Fong Lin 2, Yaping Tu 1*

1 Creighton University School of Medicine 2 University of Nebraska Medical Center

* Address correspondence to: E-mail: yat60399{at}creighton.edu

Abstract

Acquisition of androgen independence by prostate cancer is the key problem of prostate cancer progression. The neuropeptide, vasoactive intestinal peptide (VIP), may act as a survival factor for prostate cancer cells under androgen deprivation. However, the molecular mechanisms by which VIP promotes the androgen-independent growth of androgen-sensitive prostate cancer cells have not been addressed. We therefore investigated the biological effect and signal pathway of VIP in LNCaP cells, a prostate cancer cell line that requires androgens for growth. We showed that low nanomolar concentrations of VIP, acting through Gs-protein coupled VIP receptors, can induce LNCaP cell growth in the absence of androgen. Blockade of androgen-receptor (AR) in these cells by AR antagonist bicalutamide, or by anti-AR small interfering RNA (siRNA), inhibited the proliferative effect of VIP. In addition, VIP stimulated androgen-independent activation of AR with an EC50 of 3.0 ± 0.8 nM. We then investigated VIP-stimulated signaling events that may interact with the AR pathway in prostate cancer cells. VIP regulation of AR activation, mediated by VIP receptors, was PKA-dependent and ERK1/2 activation contributes to VIP-mediated AR activation. Furthermore, PKA-dependent Rap1 activation is required for both ERK1/2 activation and androgen-independent AR activation in LNCaP cells upon VIP stimulation. Finally, we showed that VIP-induced AR activation was also present in prostate cancer CWR22Rv1 and PC3 cells transfected with the wild-type AR. Altogether, we demonstrate that VIP acting through its Gs-protein coupled receptors can cause androgen-independent transactivation of AR through a PKA/Rap1/ERK1/2 pathway, thus promoting androgen-independent proliferation of androgen-sensitive prostate cancer cells.


Key words: VIP/PACAP, Sex hormones, Gs family, Protein Kinase A, MAP Kinase


This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
L. S. Lyons, S. Rao, W. Balkan, J. Faysal, C. A. Maiorino, and K. L. Burnstein
Ligand-Independent Activation of Androgen Receptors by Rho GTPase Signaling in Prostate Cancer
Mol. Endocrinol., March 1, 2008; 22(3): 597 - 608.
[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 © 2007 by the American Society for Pharmacology and Experimental Therapeutics