title: Role of ERK/MAP kinase in mitogenic interaction between ACTH and FGF2 in mouse Y1 adrenocortical tumor cells.
abstract: In G0/G1 cell cycle-arrested Y1 adrenocortical cells FGF2 is a strong mitogen, whereas ACTH39 can be a weak mitogen or a strong anti-mitogenic agent. Phosphorylated ERK1/2-MAP kinases are undetectable by Western and immunocitochemistry assay in G0/G1-arrested Y1 adrenal cells. Cell entry into S phase linearly correlates with migration of phosphorylated ERK to nucleus. FGF2 rapid and strongly triggers transient phosphorylation of ERK1/2, whereas ACTH39 is a poor ERK1/2 activator. But, the MEK1 inhibitor, PD98059 (50microM), inhibits cFos and cyclin D1 induction and DNA synthesis stimulation by both ACTH39 and FGF2, suggesting that ERK1/2 activation mediates the strong and the weak mitogenic effect of, respectively, FGF2 and ACTH39. In addition, ACTH39 antagonizes the FGF2 mitogenic effect keeping untouched ERK1/2 activation, c-Fos and cyclin D1 induction.
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brasil.
authors.forename: C F
authors.initials: CF
authors.lastname: Lotfi
authors.forename: E T
authors.initials: ET
authors.lastname: Costa
authors.forename: T T
authors.initials: TT
authors.lastname: Schwindt
authors.forename: H A
authors.initials: HA
authors.lastname: Armelin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D008934:Mitogens / Q000494:pharmacology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D008934:Mitogens; D016760:Proto-Oncogene Proteins c-fos; D016222:Fibroblast Growth Factor 2; D019938:Cyclin D1; D000324:Adrenocorticotropic Hormone; D004247:DNA; D020928:Mitogen-Activated Protein Kinases