Uterus Hyperplasia and Increased Carcinogen-Induced Tumorigenesis in Mice Carrying a Targeted Mutation of the Chk2 Phosphorylation Site in Brca1

    October 2004 in “ Molecular and Cellular Biology ”
    Sang Soo Kim, Liu Cao, Cuiling Li, Xiaoling Xu, L. Julie Huber, Lewis A. Chodosh, Chu‐Xia Deng
    TLDR Mice with a specific BRCA1 mutation have a higher risk of tumors, especially in the uterus and ovaries.
    The study investigated the role of CHK2-dependent phosphorylation of BRCA1 by creating a mouse model with a targeted mutation (S971A) in Brca1. Unlike other Brca1 mutants, these mice were born without developmental defects but showed a moderately increased risk of spontaneous tumors, particularly uterus hyperplasia and ovarian abnormalities in females by age 2. When exposed to DNA-damaging agents, these mice exhibited increased tumorigenesis, with 80% developing tumors by age 1, including lymphoma, mammary, and endometrial tumors. The Brca1(S971A/S971A) cells had a reduced ability to activate the G(2)/M cell cycle checkpoint and stabilize p53, indicating that Chk2 phosphorylation of S971 played a crucial role in DNA damage response and tumor suppression.
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