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ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity.


ABSTRACT: MED1 is a key coactivator of 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 cancer have remained unclear. Here, we report that MED1 is overexpressed in the epithelium of clinically localized human prostate cancer patients, which correlated with elevated cellular proliferation. In a Nkx3.1:Pten mutant mouse model of prostate cancer that recapitulates the human disease, MED1 protein levels were markedly elevated in the epithelium of both invasive and castration-resistant adenocarcinoma prostate tissues. Mechanistic evidence showed that hyperactivated ERK and/or AKT signaling pathways promoted MED1 overexpression in prostate cancer cells. Notably, ectopic MED1 overexpression in prostate cancer xenografts significantly promoted tumor growth in nude mice. Furthermore, MED1 expression in prostate cancer cells promoted the expression of a number of novel genes involved in inflammation, cell proliferation, and survival. Together, these findings suggest that elevated MED1 is a critical molecular event associated with prostate oncogenesis.

SUBMITTER: Jin F 

PROVIDER: S-EPMC5838364 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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ERK and AKT signaling drive MED1 overexpression in prostate cancer in association with elevated proliferation and tumorigenicity.

Jin Feng F   Irshad Shazia S   Yu Wei W   Belakavadi Madesh M   Chekmareva Marina M   Ittmann Michael M MM   Abate-Shen Cory C   Fondell Joseph D JD  

Molecular cancer research : MCR 20130328 7


MED1 is a key coactivator of 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 cancer have remained unclear. Here, we report that MED1 is overexpressed in the epithelium of clinically loca  ...[more]

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