Accession Number : ADA454874


Title :   Clinic and Functional Analysis of p73R1 Mutations in Prostate Cancer


Descriptive Note : Annual rept. 1 Jan 2005-14 Jan 2006


Corporate Author : MAYO FOUNDATION ROCHESTER MN


Personal Author(s) : Liu, Wanguo


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA454874


Report Date : FEB 2006


Pagination or Media Count : 40


Abstract : 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.


Descriptors :   *DEOXYRIBONUCLEIC ACIDS , *PROSTATE CANCER , *APOPTOSIS , RISK , MUTATIONS , GENES , LOSSES , CELLS(BIOLOGY) , PROSTATE GLAND , MITOCHONDRIA , BLOOD PROTEINS , GENETICS , RESPONSE(BIOLOGY) , MALES , FUNCTIONAL ANALYSIS , DAMAGE


Subject Categories : BIOCHEMISRTY
      ANATOMY AND PHYSIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE