|Reference : Stimulation of the 92-Kd Type Iv Collagenase Promoter and Enzyme Expression in Human ...|
|Scientific journals : Article|
|Human health sciences : Oncology|
|Stimulation of the 92-Kd Type Iv Collagenase Promoter and Enzyme Expression in Human Melanoma Cells|
|Lauricella-Lefebvre, M. A. [> > > >]|
|Castronovo, Vincenzo [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]|
|Sato, H. [> > > >]|
|Seiki, M. [> > > >]|
|French, D. L. [> > > >]|
|Merville, Marie-Paule [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]|
|Invasion & Metastasis|
|Yes (verified by ORBi)|
|[en] The 92-kD type IV collagenase is a member of the metalloproteinase family which degrades type IV collagen, a major component of basement membrane and is involved in tumor invasion and metastasis. The promoter and adjacent regulatory sequences of the 92-kD type IV collagenase have been identified previously and three cis-acting elements homologous to the binding sites for AP-1, NF-KB and SP-1 proteins contributed to induction of the promoter activity by 12-O-tetradecanoylphorbol 13-acetate (TPA) and tumor necrosis factor (TNF-alpha) in HT1080 cells. To date, no direct correlation between promoter activity and expression of the 92-kD type IV collagenase has been reported in normal or cancer cells. In this study, the effects of the transcriptional stimulation of the 92-kD type IV collagenase gene on the expression of the enzyme in human A2058 melanoma cells was analyzed by zymography experiments. Quantitative immunoblots using a monoclonal antibody that recognized specifically and exclusively the 92-kD type IV collagenase, confirmed that the 92-kD gelatinase was 92-kD type IV collagenase. Stimulation of the promoter activity resulted in increased gelatinase activity in the culture medium of A2058 cells. A direct correlation between TPA- and TNF-alpha-mediated promoter stimulation of the 92-kD type IV collagenase gene and its expression was also demonstrated in the human fibrosarcoma HT1080 cells. Interleukin-1 alpha failed to induce 92-kD gene promoter activity and type IV collagenase expression in melanoma and fibrosarcoma cell lines. Our data demonstrated that TPA- and TNF-alpha-induced 92-kD type IV collagenase promoter stimulation leads to a proportional increase of enzyme expression and secretion and thus could contribute to the activation of the invasive phenotype.|
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