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Tumor promoter-induced MMP-13 gene expression in a model of initiated epidermis.

Authors
  • Zeliadt, Nicholette A
  • Warmka, Janel K
  • Winston, Susanna E
  • Kahler, Rachel
  • Westendorf, Jennifer J
  • Mauro, Laura J
  • Wattenberg, Elizabeth V
Type
Published Article
Journal
Biochemical and biophysical research communications
Publication Date
Apr 30, 2004
Volume
317
Issue
2
Pages
570–577
Identifiers
PMID: 15063796
Source
Medline
License
Unknown

Abstract

In mouse epidermis in vivo, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increases gene expression of matrix metalloproteinase-13 (MMP-13), an enzyme implicated in carcinogenesis. Here we used a keratinocyte cell line (308) derived from initiated mouse skin to investigate TPA-induced MMP-13 gene expression. Use of a pharmacological inhibitor (U0126) demonstrated that extracellular signal regulated kinase (ERK) plays a major role in TPA-induced MMP-13 gene expression. The 5'-flanking sequences of the MMP-13 gene contain binding sites for activator protein-1 (AP-1) and Runx. Both transcription factor families can be modulated by ERK and have been implicated in MMP-13 gene expression. TPA stimulated ERK-dependent increases in c-Fos protein and the c-Fos content of AP-1 complexes. MMP-13 promoter studies indicated that TPA requires AP-1, but not Runx, to induce MMP-13 gene expression. These studies show that in mouse keratinocytes MMP-13 gene expression can be induced through a Runx-independent pathway that involves the ERK-dependent modulation of AP-1.

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