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Involvement of MyoD and c-myb in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene

  • Preclinical study
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Abstract

BRCA1 is closely related to the pathogenesis of breast cancer, BRCA1 mRNA is reduced in sporadic breast cancer cells despite the lack of mutations. In the present report, we find that MyoD expression and BRCA1 expression is correlated in sporadic breast tumors, overexpression of MyoD and c-myb stimulates BRCA1 expression, knockdown of MyoD and c-myb attenuates BRCA1 expression and attenuates the ability of BRCA1 to protect cells against hydrogen peroxide. MyoD and c-myb interact with p300 and PCAF, forming activating transcriptional complexes which bind to E-box and c-myb sites on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Regulation of BRCA1 expression by MyoD and c-myb complexes may be part of an integral signaling pathway that determines and explains breast cancer susceptibility. Detection expression status of the various proteins in these complexes may predispose to the onset of sporadic breast cancer.

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Abbreviations

E2:

17β-estradiol

HAT:

Histone acetyltransferase

PBS:

Phosphate-buffered saline

FBS:

Fetal bovine serum

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Acknowledgments

The work was supported by the grants from Shanghai Pujiang Program (2008); Innovation Program of Shanghai Municipal Education Commission (No. 09ZZ04); the National Basic Research Program of China (2006CB910501); National Natural Science Foundation of China (30371580, 30572109); the Natural Science Foundation of Shanghai (No. 09ZR1406900); the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.

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Authors and Affiliations

  1. Department of Breast Surgery, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road Road, Shanghai, 200032, People’s Republic of China

    Wei Jin, Li Chen, Gen-hong Di, Hong Ling, Jiong Wu & Zhi-ming Shao

  2. School of Life Science, Liaoning Normal University, 850 Huanghe Road, Dalian, 116029, People’s Republic of China

    Yang Liu

  3. Department of Pharmacology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ, 08903, USA

    Hua Zhu

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  1. Wei Jin
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  2. Yang Liu
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  3. Li Chen
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  4. Hua Zhu
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Correspondence to Zhi-ming Shao.

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Wei Jin and Yang Liu contributed equally to the present study.

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Jin, W., Liu, Y., Chen, L. et al. Involvement of MyoD and c-myb in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene. Breast Cancer Res Treat 125, 699–713 (2011). https://doi.org/10.1007/s10549-010-0876-1

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