Accession Number:

ADA543733

Title:

Activation of Hh Signaling: A Critical Biological Consequence of ETS Gene Anomalies in Prostate Cancer

Descriptive Note:

Annual summary 1 Mar 2010-28 Feb 2011

Corporate Author:

ORDWAY RESEARCH INST ALBANY NY

Personal Author(s):

Report Date:

2011-03-31

Pagination or Media Count:

9.0

Abstract:

One of the more notable early molecular changes in prostate cells associated with neoplastic development involves the acquisition of genetic anomalies chromosomal rearrangements or deletions that increase expression of gene products of the ETS family exemplified by ERG, ETV-1, ETV-4 or ELK-4. We propose that one important consequence of ETS gene overexpression in prostate cells is increased expression and activity of Gli transcription factors that are normally induced by classical Hedgehog signaling. To this end, we have identified that GLI1 is regulated by androgens in both LNCaP and VCaP prostate cancer cells. We also under the process of generating the ETS-overexpressing benign prostate cells to test the consequences of ETS overexpression on hedgehog signaling. Additionally, we identified Gli overexpression induces androgen-independent growth of prostate cancer cells and this action is mediated by interaction between GLIs and androgen receptor AR which leads to activation of AR signaling under androgen-deprived conditions.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE