BRCA1–Sp1 interactions in transcriptional regulation of the IGF‐IR gene

FEBS Letters

Glaser, Tova¹  Ouchi, Toru²  Werner, Haim¹  Abramovitch, Shirley¹ 

[1] Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, NY 10029, USA

关键词: Insulin-like growth factor;    Insulin-like growth factor-I receptor;    BRCA1;    Sp1;    Breast cancer;   

DOI  :  10.1016/S0014-5793(03)00315-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown