Activation of Hh Signaling: A Critical Biological Consequence of ETS Gene Anomalies in Prostate Cancer
Annual rept. 1 Mar 2011-31 Dec 2012
SOUTH CAROLINA UNIV COLUMBIA
Pagination or Media Count:
One of the most 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. In this study, we have identified that GLI1 is regulated by androgens in both LNCaP and VCaP prostate cancer cells. We also identified Gli overexpression induces androgen-independent growth of prostate cancer cells and this action is mediated by a direct interaction between GLIs and androgen receptor AR which leads to enhanced AR signaling under both androgen-supplemented and androgen-deprived conditions. Additionally we discovered CDK819 as novel regulators of AR-mediated transcription in prostate cancer cells, which may provide helpful information in developing effective treatment of advanced prostate cancer in near future.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research