title: 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.
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-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.
authors.affiliation: Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: S
authors.initials: S
authors.lastname: Ichigo
authors.forename: S
authors.initials: S
authors.lastname: Morishita
authors.forename: T
authors.initials: T
authors.lastname: Tamaya
mesh_terms: D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D016758:Genes, jun / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004967:Estrogens; D012333:RNA, Messenger; D011493:Protein Kinase C