INSULIN IGF-1 MODULATION OF THE EXPRESSION OF 2 ESTROGEN-INDUCED GENES IN MCF-7 CELLS/

Estrogen responses of human breast cancer cell lines have frequently b een shown to be promoted by insulin. We have examined the action of in sulin, and its interaction with estradiol, in regulating the expressio n of the estrogen-induced genes, LIV-1 and pS2. Both hormones cause in creases in mRNA levels of the two genes but do so by distinct mechanis ms. The concentration of insulin required to produce this effect sugge sts that it is acting via its ability to bind to the IGF-1 receptor. B oth insulin and estradiol exert their effects at the level of transcri ption. Induction by insulin is dependent upon continued protein synthe sis whereas induction by estradiol is not. Induction by both insulin a nd estradiol is prevented by the pure antiestrogen, ICI 164384, indica ting the requirement for an activatable estrogen receptor. Insulin doe s not stimulate LIV-1 expression via the androgen receptor. These resu lts demonstrate that both estradiol and insulin can stimulate the tran scription of these estrogen-inducible genes, by separate mechanisms bo th of which involve the estrogen receptor.