Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Cellular, Molecular, and Tumor Biology 52: Molecular Alterations in Prostate Cancer

The inhibitory effect of a tumor suppressor (DOC-2/DAB2) on androgen receptor-mediated non-genomic signal pathway in prostatic cancer

Jian Zhou, Gina Hernandez and Jer-Tsong Hsieh
Jian Zhou
UT Southwestern Medical Ctr., Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gina Hernandez
UT Southwestern Medical Ctr., Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jer-Tsong Hsieh
UT Southwestern Medical Ctr., Dallas, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published April 2004
  • Article
  • Info & Metrics
Loading
Proc Amer Assoc Cancer Res, Volume 45, 2004

Abstract

2680

Androgen is known to be a key mitogen factor for the growth of prostate cancer. Androgenic effect is mediated through its specific receptor as a transcription factor. However, recent studies indicate that androgen receptor (AR) can function via non-genomic pathway by activating non-receptor tyrosine kinase such as Src and subsequent down stream signal pathway such as MAPK, which results in cell proliferation of prostate cancer (PCa). In PCa, DOC-2/DAB2 appears to be a potent tumor suppressor in prostate by directly inhibiting the function of several signaling molecules containing SH3 domain including Grb2 and Src. Thus, we decided to investigate the effect of DOC-2/DAB2 on AR-mediated signal transduction in PCa. Previous data demonstrate that the treatment of Src inhibitor can suppress the androgen-induced cell proliferation in LNCaP cell line, indicating that the Src activation is involved in the AR-mediated cell proliferation. Also, the inhibition on the AR-mediated cell proliferation of LNCaP subline was found in cells transfected with DOC-2/DAB2. On the other hand, we studied a normal human prostate cell line PZ-HPV7 expressing endogenous DOC-2/DAB2 protein and AR and we found that the proliferation of PZ-HPV7 cell could be stimulated by androgen in a dose-dependent manner. By transfecting PZ-HPV7 with an interference RNA targeting DOC-2/DAB2 mRNA specifically, we observed a further enhancement of AR-induced cell proliferation in this cell line. The data indicate that DOC-2/DAB2 plays a central role in modulating AR effect in normal prostatic epithelium. To understand the underlying mechanism, we were able to demonstrate that the AR-induced activation of Src, determined by a specific anti-phosphorylated Src (tyrosine416) antibody, which could be suppressed in PCa cells expressing DOC-2/DAB2 protein. Subsequently, the down stream MAPK pathway such as Erk2 was also suppressed by DOC-2/DAB2. To demonstrate the interruption between the physical interaction of Src protein and AR by DOC-2/DAB2, a pull-down experiment was conducted using GST-Src (SH3 domain) fusion protein in which the interaction between AR and Src could be blocked by an increasing amount of DOC-2/DAB2. To examine whether DOC-2/DAB2 could modulate the transcription activity of AR, we found that DOC-2/DAB2 did not the promoter activity of PSA induced by androgen. Thus, our data demonstrate that DOC-2/DAB2 can modulate the AR-induced cell proliferation in PCa via the non-genomic pathway of AR by competing the binding to Src. Taken together, we believe that DOC-2/DAB2 is a key homeostatic factor to balance the mitogenic signal in normal prostatic epithelium.

  • American Association for Cancer Research
Previous
Back to top
April 2004
Volume 64, Issue 7 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The inhibitory effect of a tumor suppressor (DOC-2/DAB2) on androgen receptor-mediated non-genomic signal pathway in prostatic cancer
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
The inhibitory effect of a tumor suppressor (DOC-2/DAB2) on androgen receptor-mediated non-genomic signal pathway in prostatic cancer
Jian Zhou, Gina Hernandez and Jer-Tsong Hsieh
Cancer Res April 1 2004 (64) (7 Supplement) 618-619;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The inhibitory effect of a tumor suppressor (DOC-2/DAB2) on androgen receptor-mediated non-genomic signal pathway in prostatic cancer
Jian Zhou, Gina Hernandez and Jer-Tsong Hsieh
Cancer Res April 1 2004 (64) (7 Supplement) 618-619;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Differential expression of class 3 semaphorins in prostate cancer cell lines
  • ZNF185, a LIM-domain protein, is a candidate tumor suppressor in prostate cancer and functions in focal adhesion pathway
  • Down-regulation of tumor suppressor, KiSS-1, in human prostate cancer cells and prostate tumours by hepatocyte growth factor/scatter factor (HGF/SF)
Show more Cellular, Molecular, and Tumor Biology 52: Molecular Alterations in Prostate Cancer
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement