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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Apr 30 2004|
Bibliographical noteFunding Information:
We thank Dr. Stuart Yuspa for contributing the 308 cell line and Dr. John A. Hassel for contributing the plasmid pRSV-PEA3. This work was supported by Research Project Grant #RPG-00-290-01-TBE from the American Cancer Society.
- Extracellular signal regulated kinase
- Matrix metalloproteinase- 13