Dossier “Breast cancer”
Insulin-like growth factors and breast cancer

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Summary

Several years of research have indicated that the insulin-like growth factor (IGF) family of ligands, receptors and binding proteins are expressed in human breast cancer. The ligands are potent mitogens for breast cancer cell lines, and blockade of IGF signaling inhibits tumor growth. The IGFs can be regulated in normal and neoplastic tissue, indicating their important role in proliferation. For example, estrogen, a hormone important in the growth and progression of breast cancer is able to alter expression of IGF ligands, receptors and binding proteins. In addition, recent data now indicate that IGF ligands can also activate estrogen receptor (ER) in a ligand-independent manner. The apparent cross-talk between IGF and ER signaling is especially important to consider since anti-estrogens, such as tamoxifen, are a major modality for the treatment of breast cancer. Recent data suggest that IGFs may also be involved in tamoxifen resistance, through upregulation of the IGF-I receptor. Thus blockade of IGF signaling in combination with tamoxifen may prove to be a beneficial treatment for breast cancer patients.

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  • Cited by (90)

    • Clinical studies in humans targeting the various components of the IGF system show lack of efficacy in the treatment of cancer

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      Citation Excerpt :

      Moreover, its expression is required for neoplastic transformation by a number of cellular oncogenes, suggesting an obligatory role between expression of functional IGF-IR and the achievement of a transformed phenotype in a variety of tumorigenesis models [1,14–18]. Furthermore, in vitro [19–21] and animal models [22,23] have shown that inhibition of either the activation or expression of IGF-IR results in the suppression of cancer cell growth and tumor formation [1]. Another important issue is the fact that IGF-1 signaling confers resistance to many anti-neoplastic therapies, while IGF-1 deficient mice exhibit greatly reduced capacity to support cancer growth and metastasis [24–27].

    • Chimaphilin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines through insulin-like growth factor-I receptor (IGF-IR) signaling

      2015, Chemico-Biological Interactions
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      Our results indicated a crucial role of the IGF-IR in drug-sensitive and drug-resistant osteosarcoma cell lines. Activation of the IGF-IR promotes proliferation and transformation as well as cell–cell and cell-substrate interactions in cancer cells [17,18]. Conversely, the blockade of IGF signaling results in the inhibition of tumor growth [19].

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