Differential expression and signaling activation of insulin receptor isoforms A and B: A link between breast cancer and diabetes

Growth Factors. 2011 Dec;29(6):278-89. doi: 10.3109/08977194.2011.616200. Epub 2011 Sep 13.

Abstract

We showed that when insulin-like growth factor II (IGF-II) is highly expressed in breast tissues and cell lines, the IGF-I receptor signaling pathway is highly activated. Since IGF-II activates the insulin receptor (INSR), we propose that the INSR signaling is also activated in this system. We examined the expression of both INSR isoforms, insulin receptor A (INSR-A) and insulin receptor B (INSR-B), and the downstream signaling pathways in breast cancer (BC) cells and in paired (normal/tumor) breast tissues from 100 patients. Analysis was performed by real-time PCR, Western blot, immunohistochemistry, and phospho-ELISA techniques. Tumor tissues and cell lines from African-American patients expressed higher levels of INSR-A, but lower levels of INSR-B. Accordingly, insulin receptor substrate 1 and focal adhesion kinase activation were significantly increased in these women. We conclude that higher INSR-A and lower INSR-B contribute to higher proliferation and lower metabolic response. Thus, differential expression of INSR isoforms represents a potential biological link between BC and diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Black or African American
  • Breast / metabolism
  • Breast Neoplasms / metabolism*
  • Diabetes Mellitus / metabolism*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / biosynthesis
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Phosphorylation
  • Protein Isoforms / metabolism
  • Receptor, Insulin / biosynthesis
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Signal Transduction*
  • Tumor Cells, Cultured
  • White People

Substances

  • Antigens, CD
  • Protein Isoforms
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • INSR protein, human
  • Receptor, Insulin
  • Focal Adhesion Protein-Tyrosine Kinases