Clinic and Functional Analysis of P73R1 Mutations in Prostate Cancer

Download or read book Clinic and Functional Analysis of P73R1 Mutations in Prostate Cancer written by and published by . This book was released on 2006 with total page 40 pages. Available in PDF, EPUB and Kindle. Book excerpt: The DNA damage-signaling pathway has been implicated in the development of prostate cancer since germline mutations in several genes (BRCA1, BRCA2, and CHEK2) whose products are involved in this pathway have been associated with increased risk for this cancer. We previously isolated a novel p73 up-regulated gene (p73R1) and identified p73R1 mutations in prostate cancer. In this report, we screened 856 unselected prostate cancer specimens and detected a frequency of 2.6% (221856) truncation mutations in prostate cancers in contrast to 0.6% (21327) in 327 population-based controls (Fishers exact test, P = 0.036), with an odds ratio of 4.3 (95% confidence interval 1.2 - 21.2). In addition, we also demonstrated that mutant p73R1 was unable to induce apoptosis and suppress cell growth in HeLa and Cos7 cells. The loss of function mutation in p73R1 is due to the inability of the mutant to induce cytochrome c release from mitochondria. These results suggest that loss of function mutations in p73R1 predispose men to prostate cancer and further support the concept that the genetic defects in the DNA damage-response genes play an important role in the development of prostate cancer.