Abstract
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-isoqrrinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) abolished estrogen-inducible over-expression of c-fos arid c-jun. The combination of both estradiol and TPA at maximum effective concentration exerted no additive and syneugistic 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.