ESTROGEN INDUCES C-HA-RAS EXPRESSION IN THE FIBROBLASTS DERIVED FROM HUMAN UTERINE ENDOMETRIUM

In this preliminary study, fibroblasts derived from uterine endometrium as a substitute for normal endometrial stroma were used to analyse the stromal role in uterine endometrium, which depends on oestrogen for growth. C-Ha-ras expression and tyrosine kinase (TK) activity in the fibroblasts were increased by oestradiol, and the increase was diminished by progesterone. Epidermal growth factor (EGF), an activator of TK, also increased c-Ha-ras expression. The combination of both oestradiol and EGF at maximum effective concentration exerted no additive and synergistic effect on induction of c-Ha-ras expression. Pretreatment with tyrphostin, an inhibitor of TK, abolished the oestrogen-inducible expression of c-Ha-ras. Oestrogen might lead to rapid induction of c-Ha-ras expression in endometrial stroma, at least in part, via the activation of TK for the early stages of oestrogen dependent growth in endometrium.