Regulation of Med1 protein by overexpression of BAP1 in breast cancer cells.

Med1 binds to a nuclear receptor and regulates transcription. Elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancers. Med1 protein expression was investigated by deubiquitinating enzymes (DUBs) overexpression in breast cancer cell lines. Various DNA constructs of SRT-DUBs were overexpressed in the MCF7 cell line, and Med1 protein expression was investigated by western blotting. The cell growth and in vitro invasion assay were performed in BRCA1-associated protein 1 (BAP1) wild type and mutant (C91A) overexpressed cells. Ubiquitination of the Med1 protein was observed, and Med1 protein expression and transcriptional activity were verified by various DUBs overexpressed. Although Med1 protein expression increased upon the overexpression of BAP1, it was not affected by the overexpression of BAP1 mutant (C91A). BAP1 was increased by the E2 treatment, which has an important effect on the breast cancer growth, and cell growth was decreased by BAP1 C91A overexpression. However, metastatic capacities were decreased by BAP1. In addition, the binding between the Med1 and the BAP1 protein was observed. These data suggested that BAP1 regulated Med1 protein expression in breast cancer cells and involved in cancer cell growth and metastasis by binding to Med1 protein.

Kim H 《Molecular & Cellular Oncology》

BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5.

Qin J ，Zhou Z ，Chen W ，Wang C ，Zhang H ，Ge G ，Shao M ，You D ，Fan Z ，Xia H ，Liu R ，Chen C ... -  《Nature Communications》

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

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.

Jin F ，Irshad S ，Yu W ，Belakavadi M ，Chekmareva M ，Ittmann MM ，Abate-Shen C ，Fondell JD ... -  《-》

BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization.

Ventii KH ，Devi NS ，Friedrich KL ，Chernova TA ，Tighiouart M ，Van Meir EG ，Wilkinson KD ... -  《-》

BAP1 functions as a tumor promoter in prostate cancer cells through EMT regulation.

Park CM ，Lee JE ，Kim JH 《-》