Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer.

摘要

Mutations in mitochondrial DNA (mtDNA) are frequent in prostate cancer and they seem to occur early during prostate malignant transformation. Depletion of mtDNA in prostate cancer cells has been linked to acquisition of androgenindependence, progression to an invasive phenotype that is resistant to conventional chemotherapies, as well as induction of epithelial-mesenchymal transition leading to cancer metastasis. Using long-range genomic polymerase chain reaction, large deletion of mtDNA can be detected in prostate cancer tissues but not benign or normal prostate tissues. Noticeably, our study excludes the germ-line origin of the mutant mtDNA pattern in prostate cancer patient through analysis of the blood of the corresponding patient. Our data conclude that mtDNA deletion is due to carcinogenesis process in somatic prostate cells. In addition, our data have unveiled the molecular alteration in prostate cancer cells resulted from mtDNA deletion. For example, Skp2 protein elevation is often associated in prostate cells with loss of mtDNA. Also, the presence of Skp2 expression can decrease the expression of BRCA2 protein as an early biomarker of prostate neoplastic transformation, which is due to BRCA2 proteolysis.