Regulation of c-fos and c-jun expression by calcitonin in human breast cancer cells.
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.
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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.
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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
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