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• W2040856720 abstract "The breast cancer-associated gene 1 (BRCA1) is the most frequently mutated tumor suppressor gene in familial breast cancers. Mutations in BRCA1 also predispose to other types of cancers, pointing to a fundamental role of this pathway in tumor suppression and emphasizing the need for effective chemoprevention in these high-risk patients. Because the methyl ester of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me) is a potent chemopreventive agent, we tested its efficacy in a highly relevant mouse model of BRCA1-mutated breast cancer. Beginning at 12 weeks of age, Brca1(Co/Co); MMTV-Cre;p53(+/-) mice were fed powdered control diet or diet containing CDDO-Me (50 mg/kg diet). CDDO-Me significantly (P < 0.05) delayed tumor development in the Brca1-mutated mice by an average of 5.2 weeks. We also observed that levels of ErbB2, p-ErbB2, and cyclin D1 increased in a time-dependent manner in the mammary glands in Brca1-deficient mice, and CDDO-Me inhibited the constitutive phosphorylation of ErbB2 in tumor tissues from these mice. In BRCA1-deficient cell lines, the triterpenoids directly interacted with ErbB2, decreased constitutive phosphorylation of ErbB2, inhibited proliferation, and induced G(0)-G(1) arrest. These results suggest that CDDO-Me has the potential to prevent BRCA1-mutated breast cancer." @default.
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• W2040856720 date "2012-01-01" @default.
• W2040856720 modified "2023-09-28" @default.
• W2040856720 title "CDDO-Methyl Ester Delays Breast Cancer Development in <i>Brca1</i>-Mutated Mice" @default.
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• W2040856720 doi "https://doi.org/10.1158/1940-6207.capr-11-0359" @default.
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