Function of the IGF-I receptor in breast cancer

J Mammary Gland Biol Neoplasia. 2000 Jan;5(1):95-105. doi: 10.1023/a:1009523501499.


The insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase regulating various biological processes such as proliferation, survival, transformation, differentiation, cell-cell and cell-substrate interactions. Different signaling pathways may underlie these pleiotropic effects. The specific pathways engaged depend on the number of activated IGF-IRs, availability of intracellular signal transducers, the action of negative regulators, and is influenced by extracellular modulators. Experimental and clinical data implicate the IGF-IR in breast cancer etiology. There is strong evidence linking hyperactivation of the IGF-IR with the early stages of breast cancer. In primary breast tumors, the IGF-IR is overexpressed and hyperphosphorylated, which correlates with radio-resistance and tumor recurrence. In vitro, the IGF-IR is often required for mitogenesis and transformation, and its overexpression or activation counteract effects of various pro-apoptotic treatments. In hormone-responsive breast cancer cells, IGF-IR function is strongly linked with estrogen receptor (ER) action. The IGF-IR and the ER are co-expressed in breast tumors. Moreover, estrogens stimulate the expression of the IGF-IR and its major signaling substrate IRS-1, while antiestrogens downregulate IGF-IR signaling, mainly by decreasing IRS-1 expression and function. On the other hand, overexpression of IRS-1 promotes estrogen-independence for growth and transformation. In ER-negative breast cancer cells, usually displaying a more aggressive phenotype, the levels of the IGF-IR and IRS-1 are often low and IGF is not mitogenic, yet the IGF-IR is still required for metastatic spread. Consequently, IGF-IR function in the late stages of breast cancer remains one of the most important questions to be addressed before rational anti-IGF-IR therapies are developed.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Breast Neoplasms / pathology*
  • Breast Neoplasms / physiopathology*
  • Female
  • Humans
  • Insulin Receptor Substrate Proteins
  • Phosphoproteins / physiology
  • Receptor, IGF Type 1 / chemistry
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology*
  • Receptors, Estrogen / physiology
  • Signal Transduction


  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Phosphoproteins
  • Receptors, Estrogen
  • Receptor, IGF Type 1