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Cancer Prevention Research
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Research Article

CDDO-Methyl Ester Delays Breast Cancer Development in Brca1-Mutated Mice

Eun-Hee Kim, Chuxia Deng, Michael B. Sporn, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams and Karen T. Liby
Eun-Hee Kim
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Chuxia Deng
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Michael B. Sporn
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Darlene B. Royce
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Renee Risingsong
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Charlotte R. Williams
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Karen T. Liby
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DOI: 10.1158/1940-6207.CAPR-11-0359 Published January 2012
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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, Brca1Co/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 G0–G1 arrest. These results suggest that CDDO-Me has the potential to prevent BRCA1-mutated breast cancer. Cancer Prev Res; 5(1); 89–97. ©2011 AACR.

  • Received July 14, 2011.
  • Revision received August 22, 2011.
  • Accepted September 13, 2011.
  • ©2011 American Association for Cancer Research.
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Cancer Prevention Research: 5 (1)
January 2012
Volume 5, Issue 1
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CDDO-Methyl Ester Delays Breast Cancer Development in Brca1-Mutated Mice
Eun-Hee Kim, Chuxia Deng, Michael B. Sporn, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams and Karen T. Liby
Cancer Prev Res January 1 2012 (5) (1) 89-97; DOI: 10.1158/1940-6207.CAPR-11-0359

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CDDO-Methyl Ester Delays Breast Cancer Development in Brca1-Mutated Mice
Eun-Hee Kim, Chuxia Deng, Michael B. Sporn, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams and Karen T. Liby
Cancer Prev Res January 1 2012 (5) (1) 89-97; DOI: 10.1158/1940-6207.CAPR-11-0359
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