Insulin receptor substrates (IRSs) and breast tumorigenesis

J Mammary Gland Biol Neoplasia. 2008 Dec;13(4):415-22. doi: 10.1007/s10911-008-9101-9. Epub 2008 Nov 22.


Insulin receptor substrate (IRS)-1 and IRS-2 are adaptor proteins in the insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) pathway that mediate cell proliferation, migration, and survival. In addition to their role as scaffolding proteins in the cytoplasm, they are able to translocate into the nucleus and regulate gene transcription. IRS levels are developmentally and hormonally regulated in the normal mammary gland and both are essential for normal mammary gland bud formation and lactation. Both IRS-1 and IRS-2 are transforming oncogenes, and induce transformation and metastasis in vitro and in vivo. In breast cancer IRSs have unique functions, with IRS-1 being mainly involved in cell proliferation and survival, whereas IRS-2 has clear roles in cell migration and metastasis. In this review we will discuss the roles of IRSs in mammary gland development and breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Cell Transformation, Neoplastic / metabolism*
  • Humans
  • Insulin Receptor Substrate Proteins / metabolism*
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Human / growth & development
  • Mammary Glands, Human / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism


  • Insulin Receptor Substrate Proteins
  • Oncogene Proteins