Insulin-like growth factor-I and estrogen interactions in breast cancer.

There is increasing evidence that estradiol and insulin-like growth factor-I (IGF-I) act through a complex cross-talk mechanism to stimulate the proliferation of normal mammary epithelium to increase the risk of breast cancer. The emerging model of cross-talk suggests that estradiol regulates the expression of IGF-I and the IGF receptor I. The subsequent binding of IGF-I to its receptor initiates an intracellular signal transduction pathway that activates transcription factors, including the estrogen receptor. Recent studies show that the effects of IGF-I on estrogen receptor activity are mediated in part by the protein kinase A and phosphatidylinositol-3-kinase/Akt pathways.