Interaction Between Estrogen Receptor Alpha and Insulin/IGF Signaling in Breast Cancer

Marilena      Lanzino; Catia      Morelli; Cecilia      Garofalo; Maria   Luisa   Panno; Loredana      Mauro; Sebastiano      Ando; Diego      Sisci

Abstract

Estrogens and insulin/Insulin like growth factor 1 (IGF-I) have potent positive effects on the proliferation of mammary epithelial cells and estrogen-dependent breast cancer cells. A cooperative crosstalk between estrogens and insulin/ IGF-I signaling pathways exists and it plays a critical role in breast carcinogenesis, tumor cell proliferation, differentiation and survival through the modulation of multiple biological events. The biological effects of estrogens are mainly mediated by the activation of estrogen receptor (ERα) whose activity is deeply influenced by the insulin/IGF-I signaling pathway. On the other hand, estrogens enhance insulin signaling by increasing the expression and/or the functional activity of some proteins involved in the insulin/IGF-I pathway. This review will focus on the critical node of the IGF-I network involved in the crosstalk with ERα and implicated in breast cancer development and progression.

Keywords: Estrogen receptor, IGF-I, IGF-IR, Shc, IRS-1, PI3K, Akt, MNAR, ErbB, EGFR