Estrogen induces expression of c-fos and c-jun via activation of protein kinase C in an endometrial cancer cell line and fibroblasts derived from human uterine endometrium.

Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cell lines (Ishikawa and HHUA cells) were analyzed for the induction manner of c-fos and c-jun transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-fos expression and protein kinase C (PKC) activity in fibroblasts and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-fos and c-jun expression and PKC activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-fos and c-jun. In these cells, 12-0-tetra-decanoylphorbol-13-acetate (TPA) increased c-fos and c-jun expression as did estradiol. Pretreatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) abolished estrogen-inducible over-expression of c-fos and c-jun. The combination of both estradiol and TPA at maximum effective concentration exerted no additive and synergistic effect on induction of c-fos and c-jun expression. In conclusion, persistent activation of PKC might lead to overexpression of c-fos and c-jun in some endometrial cancers with an estrogen predominant milieu, which might be, at least in part, associated with the transformation or growth potential.