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Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells

Oncogene volume 23, pages 5792–5798 (2004)Cite this article

Abstract

Expression of deletion mutants of the breast and ovarian cancer-specific tumor suppressor protein, BRCA1, in the mammary epithelial cell line MCF10A revealed a powerful growth suppressive effect by a mutant that has the amino-terminal 302 amino acids deleted (ΔN-BRCA1). The growth suppression is associated with an increase in apoptosis and amplification in centrosome number. The growth inhibitory effect of ΔN-BRCA1 was not observed in cervical epithelial HeLa cells, suggesting that the phenotypes of BRCA1 mutant proteins differ depending on the cell line being tested. An internal domain, including BRCA1 residues 303–1292, caused the suppression of MCF10A cell growth, and the amino terminus of BRCA1 autoinhibited the growth suppression. Single point mutations that disrupted the amino-terminal RING domain of BRCA1 caused significant suppression of growth in MCF10A cells. These results suggest that the proper function of the RING domain, likely to be ubiquitin ligase function, is important in regulating the growth of the mammary epithelial cell line and in autoregulating the powerful internal growth-inhibiting domain of the BRCA1 tumor suppressor.

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Acknowledgements

This project was supported by research Grant CA90281 from the National Cancer Institute (JDP), by fellowship DAMD17-00-0164 from the Department of Defense Breast Cancer Research Program (FY), and a grant in Aid from the Tokyo Biochemical Research Foundation and the Kanzawa Medical Research Foundation (NC).

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  1. Fanglei You

    Present address: Dana-Farber Cancer Institute, Boston, MA, USA

Authors and Affiliations

  1. Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA

    Fanglei You & Jeffrey D Parvin

  2. Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Natsuko Chiba & Chikashi Ishioka

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  1. Fanglei You
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  2. Natsuko Chiba
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Correspondence to Jeffrey D Parvin.

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You, F., Chiba, N., Ishioka, C. et al. Expression of an amino-terminal BRCA1 deletion mutant causes a dominant growth inhibition in MCF10A cells. Oncogene 23, 5792–5798 (2004). https://doi.org/10.1038/sj.onc.1207739

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