title: Lovastatin selectively inhibits ras activation of the 12-O-tetradecanoylphorbol-13-acetate response element in mammalian cells.
abstract: To evaluate ras-mediated signal transduction, an alkaline phosphatase gene (SEAP) was placed under the control of the ras-inducible phorbol ester response element (TRE) in murine fibroblasts (TRE-SEAP cells). The Kirsten ras gene was placed under the control of the glucocorticoid-inducible mouse mammary tumor virus promoter and introduced into the TRE-SEAP cells. Dexamethasone increased ras expression in the TRE-SEAP cells carrying the Kirsten ras gene and stimulated SEAP activity 25-fold. Lavostatin blocked dexamethasone induction of SEAP activity (50% inhibitory concentration, 0.5 microM) but did not affect phorbol ester-induced SEAP activity in the same cells. Lovastatin also did not block forskolin induction of SEAP activity in cells expressing SEAP under the control of the cyclic AMP response element.
authors.affiliation: Department of Cancer Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: D
authors.initials: D
authors.lastname: Defeo-Jones
authors.forename: E M
authors.initials: EM
authors.lastname: McAvoy
authors.forename: R E
authors.initials: RE
authors.lastname: Jones
authors.forename: G A
authors.initials: GA
authors.lastname: Vuocolo
authors.forename: K M
authors.initials: KM
authors.lastname: Haskell
authors.forename: R J
authors.initials: RJ
authors.lastname: Wegrzyn
authors.forename: A
authors.initials: A
authors.lastname: Oliff
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D003907:Dexamethasone; D008148:Lovastatin; D000469:Alkaline Phosphatase; D013755:Tetradecanoylphorbol Acetate