MED1 is a key coactivator for the androgen receptor (AR) and other signal-activated transcription factors.
Whereas MED1 is overexpressed in prostate cancer cell lines and is thought to coactivate distinct target genes involved in cell-cycle progression and castration-resistant growth, the underlying mechanisms by which MED1 becomes overexpressed and its oncogenic role in clinical prostate cancers have remained unclear. Here we report that MED1 is overexpressed in the epithelium of clinically localized human prostate cancer patients and that its overexpression correlates with elevated cellular proliferation. In a Nkx3.1:Pten mutant mouse model of prostate cancer that recapitulates the human disease, MED1 protein levels are markedly elevated in the epithelium of both invasive and castration-resistant adenocarcinoma prostate tissues. Evidence is presented showing that hyperactivated ERK and/or AKT signaling pathways promote MED1 overexpression in prostate cancer cells. Notably, ectopic MED1 overexpression in prostate cancer xenografts significantly promotes tumor growth in nude mice. Furthermore, ectopic overexpression of MED1 in prostate cancer cells promotes the expression of a number of novel genes involved in inflammation, cell proliferation, and survival. Together, these findings suggest that MED1 overexpression may be an important molecular event associated with prostate oncogenesis and as such, could represent a novel biomarker and target for therapeutic intervention.
Written by:
Jin F, Irshad S, Yu W, Belakavadi M, Chekmareva M, Ittmann MM, Abate-Shen C, Fondell JD. Are you the author?
Robert Wood Johnson Medical School, UMDNJ.
Reference: Mol Cancer Res. 2013 Mar 28. Epub ahead of print.
doi: 10.1158/1541-7786.MCR-12-0618
PubMed Abstract
PMID: 23538858
UroToday.com Investigative Urology Section
