TY - JOUR
T1 - BRCA1 suppresses insulin-like growth factor-I receptor promoter activity
T2 - Potential interaction between BRCA1 and Sp1
AU - Maor, Sharon B.
AU - Abramovitch, Shirley
AU - Erdos, Mike R.
AU - Brody, Lawrence C.
AU - Werner, Haim
N1 - Funding Information:
H.W. is the recipient of a Guastalla Fellowship, The Rashi Foundation, Israel, and is supported in part by Grant 3606 from the Chief Scientist’s Office of the Ministry of Health, Israel, and by Grant 438/98 from The Israel Academy of Sciences and Humanities.
PY - 2000/2
Y1 - 2000/2
N2 - The insulin-like growth factor I receptor (IGFI-R) has an important role in breast cancer etiology. The receptor is overexpressed by most breast cancers, where it functions as a potent antiapoptotic agent. BRCA1 is a tumor suppressor gene that is mutated in a large fraction of familial breast and ovarian cancers. Cotransfection of Saos-2, MCF7, and CHO cells with IGF-I-R promoter constructs driving luciferase reporter genes, and with a BRCA1 expression vector, suppressed promoter activity in a dose-dependent manner. Functional interactions between BRCA1 and Sp1 in the regulation of the IGF-I- R gene were studied in Schneider cells, a Drosophila cell line which lacks endogenous Sp1. In these cells BRCA1 suppressed 45% of the Sp1-induced trans- activation of the IGF-I-R promoter. These results suggest that BRCA1 is capable of suppressing the IGF-I-R promoter in a number of cell lines, thus resulting in low levels of receptor mRNA and protein. Mutant versions of BRCA1 lacking trans-activational activity can potentially derepress the IGF- I-R promoter. Activation of the overexpressed receptor by locally produced or circulating IGFs may be a crucial step in breast and ovarian cancer progression. (C) 2000 Academic Press.
AB - The insulin-like growth factor I receptor (IGFI-R) has an important role in breast cancer etiology. The receptor is overexpressed by most breast cancers, where it functions as a potent antiapoptotic agent. BRCA1 is a tumor suppressor gene that is mutated in a large fraction of familial breast and ovarian cancers. Cotransfection of Saos-2, MCF7, and CHO cells with IGF-I-R promoter constructs driving luciferase reporter genes, and with a BRCA1 expression vector, suppressed promoter activity in a dose-dependent manner. Functional interactions between BRCA1 and Sp1 in the regulation of the IGF-I- R gene were studied in Schneider cells, a Drosophila cell line which lacks endogenous Sp1. In these cells BRCA1 suppressed 45% of the Sp1-induced trans- activation of the IGF-I-R promoter. These results suggest that BRCA1 is capable of suppressing the IGF-I-R promoter in a number of cell lines, thus resulting in low levels of receptor mRNA and protein. Mutant versions of BRCA1 lacking trans-activational activity can potentially derepress the IGF- I-R promoter. Activation of the overexpressed receptor by locally produced or circulating IGFs may be a crucial step in breast and ovarian cancer progression. (C) 2000 Academic Press.
KW - BRCA1
KW - IGF-I receptor
KW - Sp1
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=0034033970&partnerID=8YFLogxK
U2 - 10.1006/mgme.1999.2958
DO - 10.1006/mgme.1999.2958
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AN - SCOPUS:0034033970
SN - 1096-7192
VL - 69
SP - 130
EP - 136
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 2
ER -
