Mechanism involved in genistein activation of insulin-like growth factor 1 receptor expression in human breast cancer cells

Wen Fang Chen, Quan Gui Gao, Man Sau Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

17 Citations (Scopus)

Abstract

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 1mM 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 (10-6M). 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 μg/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.
Original languageEnglish
Pages (from-to)1120-1125
Number of pages6
JournalBritish Journal of Nutrition
Volume98
Issue number6
DOIs
Publication statusPublished - 1 Dec 2007

Keywords

  • Genistein
  • Human breast cancer
  • Insulin-like growth factor 1 receptor
  • Oestrogen
  • Oestrogen receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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