BioSpace.com

Biotech and Pharmaceutical
News & Jobs
Search the Site
 
   
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Browse Biotech Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

INVESTOR
Market Summary
News
IPOs

PROFILES
Company Profiles

START UPS
Companies
Events

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Biotech Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Molecular Biology - Oncology - Urology

TGF-ß Regulates DNA Methyltransferase Expression in Prostate Cancer, Correlates with Aggressive Capabilities, and Predicts Disease Recurrence
Published: Friday, September 30, 2011
Author: Qiang Zhang et al.

by Qiang Zhang, Lin Chen, Brian T. Helfand, Thomas L. Jang, Vidit Sharma, James Kozlowski, Timothy Michael Kuzel, Lihua J. Zhu, Ximing J. Yang, Borko Javonovic, Yinglu Guo, Scott Lonning, Jay Harper, Beverly A. Teicher, Charles Brendler, Nengwang Yu, William J. Catalona, Chung Lee

Background

DNA methyltransferase (DNMT) is one of the major factors mediating the methylation of cancer related genes such as TGF-ß receptors (TßRs). This in turn may result in a loss of sensitivity to physiologic levels of TGF-ß in aggressive prostate cancer (CaP). The specific mechanisms of DNMT's role in CaP remain undetermined. In this study, we describe the mechanism of TGF-ß-mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy.

Methodology/Principal Findings

We used human CaP cell lines with varying degrees of invasive capability to describe how TGF-ß mediates the expression of DNMT in CaP, and its effects on methylation status of TGF-ß receptors and the invasive capability of CaP in vitro and in vivo. Furthermore, we determined the association between DNMT expression and clinical outcome after radical prostatectomy. We found that more aggressive CaP cells had significantly higher TGF-ß levels, increased expression of DNMT, but reduced TßRs when compared to benign prostate cells and less aggressive prostate cancer cells. Blockade of TGF-ß signaling or ERK activation (p-ERK) was associated with a dramatic decrease in the expression of DNMT, which results in a coincident increase in the expression of TßRs. Blockade of either TGF-ß signaling or DNMT dramatically decreased the invasive capabilities of CaP. Inhibition of TGF-ß in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth. Finally, independent of Gleason grade, increased DNMT1 expression was associated with biochemical recurrence following surgical treatment for prostate cancer.

Conclusions and Significance

Our findings demonstrate that CaP derived TGF-ß may induce the expression of DNMTs in CaP which is associated with methylation of its receptors and the aggressive potential of CaP. In addition, DNMTs is an independent predictor for disease recurrence after prostatectomy, and may have clinical implications for CaP prognostication and therapy.

  More...

 

//-->