BRCA1 and NORE1A Form a Her2/Ras Regulated Tumor Suppressor Complex Modulating Senescence.

ABSTRACT: BRCA1 is a tumor suppressor with a complex mode of action. Hereditary mutations in BRCA1 predispose carriers to breast cancer, and spontaneous breast cancers often exhibit defects in BRCA1 expression. However, haploinsufficiency or suppression of BRCA1 expression leads to defects in DNA repair, which can induce DNA damage responses, leading to senescence. Activating mutation or overexpression of the Her2 oncoprotein are also frequent drivers of breast cancer. Yet, over-activation of Her2, working through the RAS oncoprotein, can also induce senescence. It is thought that additional defects in the p53 and Rb tumor suppressor machinery must occur in such tumors to allow an escape from senescence, thus permitting tumor development. Although BRCA1 mutant breast cancers are usually Her2 negativ

SUBMITTER: Nelson N 

PROVIDER: S-EPMC10452424 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature