Insulin-like growth factor 1 attenuates antiestrogen- and antiprogestin-induced apoptosis in ER+ breast cancer cells by MEK1 regulation of the BH3-only pro-apoptotic protein Bim
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.