Re-expression of elafin in 21MT2 breast carcinomas by phorbol 12-myristate 13-acetate is mediated by the Ap1 site in the elafin promoter.
elafin is a unique elastase inhibitor. It is differentially expressed at the transcriptional level in human normal mammary epithelial cells and carcinomas. The elafin gene is induced by PMA in 21MT2 breast tumor cells. By deletion analysis and mutagenesis, we have identified the Ap1 site in the promoter as the cis element mediating transcriptional activation of elafin in 70N normal breast cells and its induction by phorbol 12-myristate 13-acetate (PMA) in 21MT2 breast tumors. PMA treatment induces AP1 factor expression, which binds to the Ap1 site of the elafin promoter. Mutation of this Ap1 abolishes the capability of induction by PMA. Furthermore, our data provide a basis for therapeutic manipulation of proteinase inhibitors such as elafin.
Zhang
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M
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Magit
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Pardee
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Sager
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D001665:Binding Sites; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014176:Protein Biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015842:Serine Proteinase Inhibitors; D018808:Transcription Factor AP-1; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate