title: Estrogen induces c-Ha-ras expression via activation of tyrosine kinase in uterine endometrial fibroblasts and cancer cells.
abstract: Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cells (Ishikawa and HHUA cells) were used to analyze the manner of induction of c-Ha-ras transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-Ha-ras expression and tyrosine kinase (TK) activity in fibroblast and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-Ha-ras expression and tyrosine kinase (TK) activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-Ha-ras. In these cells, epidermal growth factor (EGF) increased c-Ha-ras expression as did estradiol. Pretreatment with tyrphostin, an inhibitor of TK, abolished estrogen-inducible overexpression of c-Ha-ras. The combination of both estradiol and EGF at maximum effective concentration exerted no additive or synergistic effect on induction of c-Ha-ras expression. In conclusion, persistent activation of TK might lead to overexpression of c-Ha-ras in some endometrial cancer cells under estrogen predominant milieu, which might be 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: S
authors.initials: S
authors.lastname: Ichigo
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: S
authors.initials: S
authors.lastname: Morishita
authors.forename: T
authors.initials: T
authors.lastname: Tamaya
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D011374:Progesterone / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)