Expression pattern of matrix metalloproteinase and TIMP genes in fibroblasts derived from Ets-1 knock-out mice compared to wild-type mouse fibroblasts
pmid: 16786167
Expression pattern of matrix metalloproteinase and TIMP genes in fibroblasts derived from Ets-1 knock-out mice compared to wild-type mouse fibroblasts
Matrix-degrading proteases play a key role in normal development, wound healing, many diseases such as rheumatoid arthritis and, in particular, tumour invasion. In invasive tumours, these enzymes are expressed by fibroblasts of the tumour stroma. Their expression and activity are tightly regulated at several levels, an important one being transcription. Previous in vitro and in vivo findings pointed to a major role of the Ets-1 transcription factor for this level of regulation. In the present study, we tried to prove this role in fibroblasts. We stimulated wild-type mouse fibroblasts with physiological doses of basic fibroblast growth factor (bFGF, known to induce different proteases and expressed by tumour cells) and compared the results to those obtained in Ets-1 -/- fibroblasts derived from Ets-1 knock-out mice. We found that basal Ets-1 levels are necessary not only for a fast induction of MMPs 2, 3 and 13 by bFGF but also for maintenance of the bFGF-induced expression of tissue inhibitors of metalloproteinases (TIMPs) 1, 2 and 3, which are known not only to inhibit but also participate as activators of certain pro-MMPs.
- University of Bonn Germany
- Ludwig-Maximilians-Universität München Germany
- Pathologisches Institut Germany
Mice, Knockout, Tissue Inhibitor of Metalloproteinase-3, Tissue Inhibitor of Metalloproteinase-2, Tissue Inhibitor of Metalloproteinase-1, Transcription, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Tissue Inhibitor of Metalloproteinases, Fibroblasts, Matrix Metalloproteinases, Proto-Oncogene Protein c-ets-1, Mice, Animals, Fibroblast Growth Factor 2, Cells, Cultured
Mice, Knockout, Tissue Inhibitor of Metalloproteinase-3, Tissue Inhibitor of Metalloproteinase-2, Tissue Inhibitor of Metalloproteinase-1, Transcription, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Tissue Inhibitor of Metalloproteinases, Fibroblasts, Matrix Metalloproteinases, Proto-Oncogene Protein c-ets-1, Mice, Animals, Fibroblast Growth Factor 2, Cells, Cultured
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