Development of the new strategy targeting for the RAD51 overexpression mammary tumor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24780313
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical veterinary science
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: OCHIAI Kazuhiko 日本獣医生命科学大学, 獣医学部, 講師 (30550488)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: イヌ / 乳腺腫瘍 / BRCA2 / RAD51 / 多型 / 乳がん

Outline of Final Research Achievements

Canine BRCA2 and RAD51 genes locus has been associated with mammary tumors in female dogs. The BRCA2 protein is involved in homologous recombination repair via its interaction with RAD51 recombinase, an interaction mediated by 8 BRC repeats. Previous structural analyses of cancer-associated mutations affecting the BRC repeats have shown that the weakening of RAD51’s affinity for even 1 repeat is sufficient to increase breast cancer susceptibility. In this study, we focused on 2 previously reported canine BRCA2 mutations (T1425P and K1435R) in BRC repeat 3 (BRC3), derived from mammary tumor samples. These mutations affected the interaction of canine BRC3 with RAD51, and were considered deleterious. Two BRC3 mutations (K1440R and K1440E), reported in human breast cancer patients, occur at amino acids corresponding to those of the K1435R mutation in dogs.

Free Research Field

分子腫瘍学