Involvement of MyoD and c-myb in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene.
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.
Jin
Wei
W
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.
Liu
Yang
Y
Chen
Li
L
Zhu
Hua
H
Di
Gen-Hong
GH
Ling
Hong
H
Wu
Jiong
J
Shao
Zhi-Ming
ZM
D000107:Acetylation; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004967:Estrogens / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006657:Histones / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016296:Mutagenesis; D017570:MyoD Protein / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D004967:Estrogens; D006657:Histones; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D020598:Proto-Oncogene Proteins c-myb