Accession Number : ADA610195


Title :   Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer


Descriptive Note : Final rept. 1 May 2010-30 Apr 2014


Corporate Author : TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER


Personal Author(s) : Hsieh, Jer-Tsong


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a610195.pdf


Report Date : Jul 2014


Pagination or Media Count : 40


Abstract : 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.


Descriptors :   *PROSTATE CANCER , BLOOD , CELLS(BIOLOGY) , DEOXYRIBONUCLEIC ACIDS , DEPLETION , INDUCTION SYSTEMS , LINKAGES , MOLECULES , MUTATIONS , NEOPLASMS , NORMALITY , ONCOGENESIS , PATIENTS , PATTERNS , PROSTATE GLAND , PROTEINS , RESISTANCE , SUPPRESSION , TISSUES(BIOLOGY) , TRANSFORMATIONS , TRANSITIONS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE