Abstract
The type IV collagenases matrix metalloprotease (MMP)-2 and MMP-9 are linked with a wide array of biological activities, including tumor invasion, metastasis, and angiogenesis. Here, we report that neuropeptide hormones, which are present in prostatic adenocarcinomas, can stimulate secreted activity of MMP-9 in human prostate cancer cell lines. Northern blotting analyses demonstrated that neuropeptide stimulation lead to elevated mRNA levels of MMP-9 but not MMP-2. Further assays of MMP-9 promoter activation and a nuclear run-off indicated that neuropeptide induction of MMP-9 expression occurs at the level of transcription. These data indicate that neuropeptides can regulate MMP activity, which, in turn, could facilitate prostate cancer progression.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma
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Cell Nucleus / metabolism
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Chloramphenicol O-Acetyltransferase / biosynthesis
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Collagenases / biosynthesis*
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Collagenases / genetics
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Enzyme Induction
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Gelatinases / biosynthesis
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Male
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Metalloendopeptidases / biosynthesis
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Molecular Weight
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Neuropeptides / pharmacology*
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Promoter Regions, Genetic
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Prostatic Neoplasms
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RNA, Messenger / biosynthesis
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Recombinant Fusion Proteins / biosynthesis
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Transcription, Genetic / drug effects*
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Transfection
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Tumor Cells, Cultured
Substances
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Neuropeptides
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RNA, Messenger
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Recombinant Fusion Proteins
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Chloramphenicol O-Acetyltransferase
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Collagenases
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9