期刊
FEBS LETTERS
卷 541, 期 1-3, 页码 149-154出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(03)00315-6
关键词
insulin-like growth factor; insulin-like growth factor-I receptor; BRCA1; Sp1; breast cancer
资金
- NCI NIH HHS [R01 CA079892, R01 CA090631, CA79892, CA90631] Funding Source: Medline
The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in breast tumorigenesis and is overexpressed in most primary tumors. BRCA1 is a transcription factor involved in numerous cellular processes, including DNA damage repair, cell growth, and apoptosis. Consistent with its tumor suppressor role, we demonstrated that BRCA1 repressed the activity of co-transfected IGF-IR promoter reporter constructs in a number of breast cancer-derived cell lines. Results of electrophoretic mobility shift assay showed that BRCA1 did not exhibit any specific binding to the IGF-IR promoter, although it prevented binding of Sp1. Co-immunoprecipitation experiments demonstrated that BRCA1 action was associated with specific interaction with Sp1 protein. Furthermore, using a series of glutathione S-transferase-tagged BRCA1 fragments, we mapped the Sp1-binding domain to a segment located between aa 260 and 802. In summary, our data suggest that the IGF-IR gene is a novel downstream target for BRCA1 action. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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