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 ho rmone were developed. Since the growth stimulatory properties of the estrog ens are governed by the estrogen receptor (ER),(4) understanding the mechan isms that activate ER are highly relevant. In addition to estrogens, peptid e growth factors can also activate the ER. The insulin-like growth factors (ICFs) are potent mitogens for ER-positive breast cancer cell lines. This r eview will examine the evidence for interaction between these two pathways. The IGFs can activate the ER, while ER transcriptionally regulates genes r equired for IGF action. Moreover, blockade of ER function can inhibit IGF-m ediated mitogenesis and interruption df IGF action can similarly inhibit es trogenic stimulation of breast cancer cells. Taken together, these observat ions 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.