Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations

Cancer Lett. 2007 Nov 18;257(2):236-43. doi: 10.1016/j.canlet.2007.07.019. Epub 2007 Sep 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Binding Sites / genetics
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Female
  • Genotype
  • Humans
  • Immunohistochemistry
  • Mutation*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Sp1 Transcription Factor / metabolism
  • Time Factors
  • Transfection


  • BRCA1 Protein
  • Sp1 Transcription Factor
  • Receptor, IGF Type 1