Mechanism involved in genistein activation of insulin-like growth factor 1 receptor expression in human breast cancer cells.
Our previous studies have shown that genistein can enhance the insulin-like growth factor (IGF)-1 receptor signalling pathway via an oestrogen receptor (ER) in human breast cancer MCF-7 cells. The present study aims to investigate how genistein regulates IGF-1 receptor expression in human MCF-7 cells. Genistein at 1 microm stimulated the growth of MCF-7 cells and this effect could be completely blocked by the IGF-1 receptor antagonist JB-1, suggesting that IGF-1 receptor is essential for mediating the proliferative effects of genistein in MCF-7 cells. Genistein increased IGF-1 receptor promoter activity. This effect could be completely abolished by co-treatment of MCF-7 cells with ICI 182,780 (10- 6 m). Genistein increased IGF-1 receptor gene expression and this effect could be completely blocked by the IGF-1 receptor antagonist JB-1. Co-treatment of MCF-7 cells with cycloheximide (5 microg/ml) completely blocked the induction of IGF-1 receptor protein and mRNA expression by genistein. The results indicated that the induction of IGF-1 receptor promoter activity by genistein required the action of ER while the stimulatory actions of genistein on IGF-1 receptor expression required the activity of the IGF-1 receptor and de novo protein synthesis. These data provide evidence to support the hypothesis that the inductive effects of genistein on IGF-1 receptor expression require the cross-talk between IGF-1 receptor and the ER-dependent pathways.
Chen
Wen-Fang
WF
Department of Physiology, Medical College of Qingdao University, China. marychhk@yahoo.com
Gao
Quan-Gui
QG
Wong
Man-Sau
MS
D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D048789:Phytoestrogens / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
D020847:Estrogen Receptor Modulators; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D019833:Genistein; D017526:Receptor, IGF Type 1