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

Abstract
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 up-regulation 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 steady-state 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. UV-induced 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 up-regulation of MMPs. Our results suggest that the time course of induction of target genes, like MMPs, differs between cell types depending on the stimulus.

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