Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region, People's Republic of China.
Physiological concentration of genistein, a natural isoflavonoid phytoestrogen, stimulates human breast cancer (MCF-7) cells proliferation. In this study, we hypothesize that low concentration of genistein mimics the action of 17beta-estradiol in stimulation of MCF-7 cell growth by enhancement of IGF-I signaling pathway. Genistein, at 1 microM, stimulated the growth of MCF-7 cells. Cell cycle analysis showed that 1 micro M genistein significantly increased the S phase and decreased the G0G1 phase of MCF-7 cells. The protein and mRNA expression of IGF-I receptor (IGF-IR) and insulin receptor substrate (IRS)-1, but not Src homology/collagen protein, increased in response to 1 microM genistein in a time-dependent manner. These effects could be completely abolished by cotreatment of MCF-7 cells with estrogen antagonist ICI 182780 (1 microM) and tamoxifen (0.1 microM). Our results also showed that genistein induction of IGF-IR and IRS-1 expression resulted in enhanced tyrosine phosphorylation of IGF-IR and IRS-1 on IGF-I stimulation. Taken together, these data provide the first evidence that the IGF-IR pathway is involved in the proliferative effect of low-dose genistein in MCF-7 cells.