Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations.
The insulin-like growth factors (IGFs) play a pivotal role in breast cancer. Inherited predisposition to breast and ovarian cancer is associated with germline BRCA1/BRCA2 mutations. To evaluate the impact of BRCA1 mutations on IGF-IR gene expression, we performed an immunohistochemical analysis of IGF-IR in primary breast tumors from BRCA1 mutation ... carriers and non-carriers. Results obtained revealed a significant elevation in IGF-IR levels in tumors from BRCA1 mutation carriers compared with non-carriers. To assess the potential inhibitory role of BRCA1 on IGF-IR levels, we infected the BRCA1-deficient HCC1937 cell line with a BRCA1-encoding adenoviral vector. Results of Western blots showed that BRCA1 induced a large reduction in endogenous IGF-IR levels. Furthermore, results of chromatin immunoprecipitation assays indicated that the mechanism of action of BRCA1 involves interaction with Sp1, a potent transactivator of the IGF-IR gene. In conclusion, our data suggests that the IGF-IR gene is a physiologically relevant downstream target for BRCA1 action.
Mesh Terms:
BRCA1 Protein, Binding Sites, Blotting, Western, Breast Neoplasms, Cell Line, Tumor, Chromatin Immunoprecipitation, Female, Genotype, Humans, Immunohistochemistry, Mutation, Promoter Regions, Genetic, Protein Binding, Receptor, IGF Type 1, Sp1 Transcription Factor, Time Factors, Transfection
BRCA1 Protein, Binding Sites, Blotting, Western, Breast Neoplasms, Cell Line, Tumor, Chromatin Immunoprecipitation, Female, Genotype, Humans, Immunohistochemistry, Mutation, Promoter Regions, Genetic, Protein Binding, Receptor, IGF Type 1, Sp1 Transcription Factor, Time Factors, Transfection
Cancer Lett.
Date: Nov. 18, 2007
PubMed ID: 17766039
View in: Pubmed Google Scholar
Download Curated Data For This Publication
144595
Switch View:
- Interactions 2