Cross talk between estrogen receptor and IGF signaling in normal mammary gland development and breast cancer

Both estrogen and insulin-like growth factor-1 (IGF-I) are critical for normal mammary gland development, but are also implicated in breast cancer development and progression. Evidence that the signaling pathways utilized by these hormones interact has been shown in normal and tumorigenic cell lines, xenograft models, and breast cancer tissue. Analysis of the mechanism of interaction between estrogen and IGF-I has revealed multiple levels of cross-talk with bi-directional regulation of both pathways. Importantly, this bi-directional regulation is often in a positive manner and the resulting synergism noted between these two potent mitogens may be a critical element in the progression of breast cancer. While targeting of the estrogen receptor has shown success in the prevention and treatment of breast cancer, it is hoped that targeting of the IGF signaling pathway will yield similar beneficial results and that inhibitors of IGF signaling may be particularly useful in combination with current antiestrogen therapies. This review will focus on the evidence indicating cross-talk between estrogen and IGF-I and reveal some of the complex mechanisms that link these important pathways in breast cancer.