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

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Abstract

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.

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Authors and Affiliations

  1. Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA, USA

    Ewa Surmacz, Marina A. Guvakova, Mary K. Nolan, Roberto F. Nicosia & Laura Sciacca

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  1. Ewa Surmacz
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  2. Marina A. Guvakova
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  4. Roberto F. Nicosia
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Surmacz, E., Guvakova, M.A., Nolan, M.K. et al. Type I insulin-like growth factor receptor function in breast cancer. Breast Cancer Res Treat 47, 255–267 (1998). https://doi.org/10.1023/A:1005907101686

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