title: Regulation of c-fos and c-jun expression by calcitonin in human breast cancer cells.
abstract: Breast cancer cells (BCC) have calcitonin (CT) receptors, yet the action of the hormone on these cells is largely unknown. We found that CT produced a strong and transient time- and dose-dependent increase in c-fos mRNA in BCC lines. This event was prevented by a protein kinase A (PKA) inhibitor, H89. CT alone did not influence the expression of c-jun and of the tissue inhibitors of metalloproteases (timp) -1 and -2 mRNAs; however, it reduced the induction of these mRNAs by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA), without apparent changes in the half-life of the mRNA (measured for c-jun). Along the same line, CT reduced the c-jun induction and T-47D growth stimulation by epidermal growth factor (EGF) and insulin. These effects were mimicked by forskolin and/or prevented by H89, suggesting that PKA activation was involved. These results indicate that CT modulates in BCC the mRNA levels of two important growth-related early response genes (c-fos and c-jun) and of two other genes (timp-1 and -2) involved in the control of metastatic events.
authors.affiliation: Bone Metabolism Unit, Service de Médecine et Laboratoire d'Investigation Clinique H. J. Tagnon, Institut J. Bordet, rue Héger-Bordet 1, Université Libre de Bruxelles, B-1000 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Lacroix
authors.forename: J J
authors.initials: JJ
authors.lastname: Body
mesh_terms: D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics; D016758:Genes, jun / Q000187:drug effects* / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018003:Receptors, Calcitonin / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D006023:Glycoproteins; D007328:Insulin; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D013449:Sulfonamides; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D005576:Colforsin; D004815:Epidermal Growth Factor; D002116:Calcitonin; D008666:Metalloendopeptidases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate