Mapping of the master transcription factor MITF in prostate cancer
“Mi” transcription family members such as TFE3 and TFEB, participate in the pathogenesis of a subgroup of renal cell carcinomas, whereas MITF is key in melanocyte development and also contributes to melanoma, behaving as an oncogene when amplified and facilitating tumor invasiveness and therapy resistance when MITF levels are low. In addition, MITF plays a role in the survival and growth of clear cell sarcoma and pancreatic cancer. In prostate cancer MITF through the regulation of the heat-shock protein CRYAB has been suggested to suppress tumor initiation. However, the role of MITF in advanced therapy resistant lethal stages of the disease remains unknown. To gain insight into the gene network regulated by MITF in prostate cancer, we mapped MITF genomewide in a human prostate cancer cell line (22Rv1) by chromatin immunoprecipitation followed by ultra high-throughput sequencing. This analysis revealed the genomewide locations of MITF in prostate cancer, including the promoter of eIF3B which we further functionally validated through ChIP-PCR and luciferase reporter assays. We propose that the master regulator MITF by regulating a distinct gene network may play key roles in suppressing lethal prostate cancer pathogenesis. Overall design: MITF ChIP-Seq in human prostate cancer cell line 22Rv1