title: Expression pattern of matrix metalloproteinase and TIMP genes in fibroblasts derived from Ets-1 knock-out mice compared to wild-type mouse fibroblasts.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Bonn, 53011 Bonn, Germany.
authors.forename: Jens Claus
authors.initials: JC
authors.lastname: Hahne
authors.forename: Tanja
authors.initials: T
authors.lastname: Fuchs
authors.forename: Haddouti
authors.initials: H
authors.lastname: El Mustapha
authors.forename: Ali Fuat
authors.initials: AF
authors.lastname: Okuducu
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Bories
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases