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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Northern
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology
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Calcitonin / pharmacology*
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Carcinogens / toxicity
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Cell Division / drug effects
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Colforsin / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Epidermal Growth Factor / pharmacology
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Gene Expression Regulation, Neoplastic / genetics
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Genes, fos / drug effects*
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Genes, fos / genetics
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Genes, jun / drug effects*
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Genes, jun / genetics
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Glycoproteins / biosynthesis
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Glycoproteins / genetics
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Humans
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Insulin / pharmacology
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Isoquinolines / pharmacology
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Metalloendopeptidases / genetics
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Protein Biosynthesis
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Protein Kinase Inhibitors
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Proteins / genetics
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RNA, Messenger / metabolism
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Receptors, Calcitonin / drug effects
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Receptors, Calcitonin / metabolism
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Sulfonamides*
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Tetradecanoylphorbol Acetate / toxicity
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Tissue Inhibitor of Metalloproteinase-2
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Tissue Inhibitor of Metalloproteinases
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Tumor Cells, Cultured
Substances
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Carcinogens
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Glycoproteins
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Insulin
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Isoquinolines
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Protein Kinase Inhibitors
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Proteins
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RNA, Messenger
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Receptors, Calcitonin
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Sulfonamides
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Tissue Inhibitor of Metalloproteinases
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Tissue Inhibitor of Metalloproteinase-2
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Colforsin
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Epidermal Growth Factor
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Calcitonin
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Metalloendopeptidases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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Tetradecanoylphorbol Acetate