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M. C. Ramos, H. Steinbrenner, D. Stuhlmann, H. Sies, P. Brenneisen

Induction of MMP-10 and MMP-1 in a squamous cell carcinoma cell line by ultraviolet radiation

Ultraviolet radiation may cause non-melanoma skin cancer by genetic and epigenetic events. In this study, we investigated in a squamous cell carcinoma cell line, SCL-1, whether UV irradiation modulates the expression of matrix metalloproteinases, known to be involved in tumor progression and metastasis by degradation of extracellular matrix components. UVA or UVB irradiation of SCL-1 resulted in a rapid transcriptional upregulation and increased secretion of two members of the matrix metalloproteinase family, MMP-10 (stromelysin-2) and MMP-1 (interstitial collagenase). The increase in MMP-10 steadystate mRNA levels was detected 1 hour after UVA and 4 h after UVB irradiation, whereas MMP-1 was upregulated 4 h after UVA and 16 h after UVB irradiation of tumor cells. UVinduced phosphorylation of extracellular regulated kinases (ERK-1/2) and p38 stress kinase and increased binding of AP-1 transcription factor preceded the rapid stimulation of MMPs in SCL-1 cells. Incubation of cells with the MEK1/2 inhibitor U0126 or the p38 inhibitor SB202190 abolished the UVA and UVB mediated induction of MMP-1 and MMP-10. In conclusion, this study shows that UV irradiation of squamous cell carcinoma results in a rapid upregulation of MMPs. Our results suggest that the time course of induction of target genes, like MMPs, differs between cell types depending on the stimulus.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 385, 02/2004
Pages: 75 - 86

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