Insulin-like growth factors control the regulation of oestrogen and progesterone receptor expression by oestrogens

Abstract

Ligands for the type I insulin-like growth factor (IGF) receptor interact with oestrogens to control the proliferation of oestrogen responsive breast cancer cells. The aim of this study was to determine the involvement of ligands for the type I IGF receptor in the regulation of oestrogen receptor (OR) expression by oestrogens and antioestrogens in these cells. Oestrogen decreased OR mRNA levels in MCF-7 cells whereas it increased them in T47D, EFM-19 and ZR-75 cells. In MCF-7 cells, IGF-I and insulin lowered further OR expression in the presence of oestrogen. In the presence of IGF-I or insulin, the induction of progesterone receptor mRNA by oestradiol was considerably attenuated in MCF-7 cells, showing that the enhanced down-regulation of OR mRNA levels influenced the expression of oestrogen-regulated genes. The oestrogen agonist activity of the antioestrogens tamoxifen and ICI 182 780 for the down-regulation of OR expression in MCF-7 cells was modulated by type I IGF receptor ligands. Overall these experiments show that OR expression is differentially regulated by oestrogen in individual oestrogen-responsive breast cancer cell lines. Ligands for the type I IGF receptor can modulate regulation of OR expression by oestrogens and antioestrogens principally in cells in which oestrogens down-regulate OR expression.