Clinic and Functional Analysis of p73R1 Mutations in Prostate Cancer
Annual rept. 1 Jan 2005-14 Jan 2006
MAYO FOUNDATION ROCHESTER MN
Pagination or Media Count:
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.
- Anatomy and Physiology
- Medicine and Medical Research