Role of estrogen receptor (ER) in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation of MCF-7 breast cancer cells, and cotreatment with the phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 and the antiestrogen ICI 182780 inhibits IGF-I-induced growth. The role of estrogen receptor (ER ) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ER (iER ). The results showed that IGF-I-dependent phosphorylation of Akt and mitogen-activated protein kinase, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ER . Moreover, these same IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I-dependent activation of PI3-K or induction of cyclin D1 expression. ICI 182780 exhibits antimitogenic activity and iER inhibits G1–S-phase progression and proliferation of MCF-7 cells treated with IGF-I, suggesting that the effects of the antiestrogen are primarily related to downregulation of ER . Journal of Molecular Endocrinology (2005) 35, 433–447