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

Biol Chem. 2004 Jan;385(1):75-86. doi: 10.1515/BC.2004.010.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / enzymology*
  • Cell Line, Tumor
  • Cell Survival
  • Humans
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 10
  • Metalloendopeptidases / biosynthesis*
  • Mitogen-Activated Protein Kinase 1 / physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / physiology
  • RNA, Messenger / metabolism
  • Time Factors
  • Transcription Factor AP-1 / physiology
  • Transcription, Genetic
  • Ultraviolet Rays*
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases

Substances

  • RNA, Messenger
  • Transcription Factor AP-1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 10
  • Matrix Metalloproteinase 1