Medical Student Research Fellowship for Summer 2010

Mentor: Hsieh, Jer-Tsong
Department: Urology
Room number: J8-134
Mail Code: 9110
Phone number: 8-3990
E-mail: jt.hsieh@utsouthwestern.edu
Project title: Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer

Human subjects IRB approved project number (where applicable): 122009-031

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) basic research

Brief Description of Project: Growing evidence suggests that mutant mitochondrial DNA (mtDNA) may play an important role in drug chemosensitivity and acquisition of metastatic competence of a variety of cancers, including prostate carcinoma. Recent evidences have shown that mtDNA depletion results in increased genomic DNA double-strand breaks. The resulting genomic instability could account for the multiple phenotypic effects observed in the cells harboring mutations/depletion of mtDNA, i.e. increased migration, changes in cell growth, resistance to apoptosis, and induction of epithelial-to-mesenchymal transition. BRCA2 gene is among the few genes known to be involved in repair of DNA double-strand breaks and whose loss is directly involved in the pathogenesis of several cancers. The tumorigenic effect of BRCA2 loss has been related, at least in part, to the genomic alterations (mutations, chromosomal rearrangements, …) induced by defective DNA repair. Recent evidences demonstrate that loss of BRCA2 protein confers a significantly elevated risk of aggressive, rapidly progressing, high-grade prostate carcinoma. However, the relationship of mtDNA mutation and BRCA2 expression is still unknown in prostate cancer progression. This project is to study the relationship between mtDNA mutation and BRCA2 gene expression using prostate cell lines and prostate cancer specimens.

Previous Research Activities or Publications with Medical Students:

2005 Kit Tam
2009 Stephen Chiang