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

Abstract Med1, a subunit of the TRAP/mediator complex acts as a transcriptional regulatory mediator, binds to a nuclear receptor and regulated transcription. It is known that elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancer, whereas low expression of Med1 protein in melanoma and lung cancer increases cancer metastasis. In this study, Med1 protein expression by deubiquitinating enzymes (DUBs) overexpression was investigated in breast and lung cancer cell lines. Overexpression of BAP1 protein did not affect Med1 mRNA expression in breast cancer and lung cancer cell. However, Med1 protein expression decreased in breast cancer cells while increased in lung cancer cell lines. In addition, Med1 protein expression by overexpression of BAP1 mutant (C91A) in breast and lung cancer cells was not affected. Increased BAP1 expression increased cell growth and metastatic capacity in lung cancer cells. And overexpression of BAP1 in breast cancer cell lines increased the transcriptional regulation of estrogen receptor (ER). In addition, the binding between the Med1 and the BAP1 protein was observed. Therefore, these data suggested that BAP1 was involved in cancer cell growth and metastasis by binding to Med1 protein and regulating Med1 protein expression depending on the cancer cell types.