Breast Cancer Research and Treatment

, Volume 47, Issue 3, pp 255-267

First online:

Type I insulin-like growth factor receptor function in breast cancer

  • Ewa SurmaczAffiliated withKimmel Cancer Institute, Thomas Jefferson University
  • , Marina A. GuvakovaAffiliated withKimmel Cancer Institute, Thomas Jefferson University
  • , Mary K. NolanAffiliated withKimmel Cancer Institute, Thomas Jefferson University
  • , Roberto F. NicosiaAffiliated withKimmel Cancer Institute, Thomas Jefferson University
  • , Laura SciaccaAffiliated withKimmel Cancer Institute, Thomas Jefferson University

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Experimental evidence suggests an important role of the type I IGF receptor (IGF-IR) in breast cancer development. Breast tumors and breast cancer cell lines express the IGF-IR. IGF-IR levels are higher in cancer cells than in normal breast tissue or in benign mammary tumors. The ligands of the IGF-IR are potent mitogens promoting monolayer and anchorage-independent growth of breast cancer cells. Interference with IGF-IR activation, expression, or signaling inhibits growth and induces apoptosis in breast cancer cells. In addition, recent studies established the involvement of the IGF-IR in the regulation of breast cancer cell motility and adhesion. We have demonstrated that in MCF-7 cells, overexpression of the IGF-IR promotes E-cadherin-dependent cell aggregation, which is associated with enhanced cell proliferation and prolonged survival in three-dimensional culture.

The expression or function of the IGF-IR in breast cancer cells is modulated by different humoral factors, such as estrogen, progesterone, IGF-II, and interleukin-1. The IGF-IR and the estrogen receptor (ER) are usually co-expressed and the two signaling systems are engaged in a complex functional cross-talk controlling cell proliferation.

Despite the convincing experimental evidence, the role of the IGF-IR in breast cancer etiology, especially in metastatic progression, is still not clear. The view emerging from cellular and animal studies is that abnormally high levels of IGF-IRs may contribute to the increase of tumor mass and/or aid tumor recurrence, by promoting proliferation, cell survival, and cell-cell interactions. However, in breast cancer, except for the well established correlation with ER status, the associations of the IGF-IR with other prognostic parameters are still insufficiently documented.

breast cancer IGF-I receptor IRS-1 SHC adhesion apoptosis