Crosstalk between the insulin-like growth factors and estrogens in breast cancer

Once it was recognized that breast tumor growth was stimulated by estrogens, successful therapeutic strategies based on depriving the tumor of this hormone were developed. Since the growth stimulatory properties of the estrogens are governed by the estrogen receptor (ER), understanding the mechanisms that activate ER are highly relevant. In addition to estrogens, peptide growth factors can also activate the ER. The insulin-like growth factors (IGFs) are potent mitogens for ER-positive breast cancer cell lines. This review will examine the evidence for interaction between these two pathways. The IGFs can activate the ER, while ER transcriptionally regulates genes required for IGF action. Moreover, blockade of ER function can inhibit IGF-mediated mitogenesis and interruption of IGF action can similarly inhibit estrogenic stimulation of breast cancer cells. Taken together, these observations suggest that the two growth regulatory pathways are tightly linked and that a further understanding of the mechanism of this crosstalk could lead to new therapeutic strategies in breast cancer.