Note. The novel nucleotide sequence reported here is available at the EMBL Data Bank under accession number X90925.
Regulation of Membrane-Type Matrix Metalloproteinase-1 Expression by Growth Factors and Phorbol 12-Myristate 13-Acetate
Article first published online: 23 JUL 2004
European Journal of Biochemistry
Volume 239, Issue 2, pages 239–247, July 1996
How to Cite
Lohi, J., Lehti, K., Westermarck, J., Kähäri, V.-M. and Keski-Oja, J. (1996), Regulation of Membrane-Type Matrix Metalloproteinase-1 Expression by Growth Factors and Phorbol 12-Myristate 13-Acetate. European Journal of Biochemistry, 239: 239–247. doi: 10.1111/j.1432-1033.1996.0239u.x
- Issue published online: 23 JUL 2004
- Article first published online: 23 JUL 2004
- (Received 23 February 1996) – EJB 96 0257/1
- matrix metalloproteinase;
- membrane-type matrix metalloproteinase-1;
- 72-kDa gelatinase;
- matrix degradation;
- cell invasion
Overexpression of membrane-type matrix metalloproteinase (MT-MMP-1) results in the activation of both endogenous and exogenous 72-kDa gelatinase. To understand the effects of MT-MMP-1 on 72-kDa gelatinase activation, we analyzed its expression in human fibroblasts and HT-1080 fibrosarcoma cells. Both cell types expressed the MT-MMP-1 mRNA constitutively at a considerable level and treatment of cells with PMA enhanced the expression about 2–3-fold. Concanavalin A treatment increased MT-MMP-1 mRNA levels in fibroblasts about 4-fold. Induction of MT-MMP-1 by phorbol 12-myristate 13-acetate (PMA) required protein synthesis as shown by cycloheximide inhibition. The induction was also inhibited by dexamethasone. Analysis of MT-MMP-1 mRNA stability using actinomycin D indicated that the half-life was rather long and not affected by PMA, suggesting transcriptional regulation. Only HT-1080 cells had significant 72-kDa gelatinase processing activity after treatment with PMA or concanavalin A, while fibroblasts were virtually negative. Immunoblotting analysis of fibroblast lysates indicated that MT-MMP-1 was present mainly in a 60-kDa form. PMA and concanavalin A caused 2–4-fold increases in its protein levels, while in HT-1080 cells PMA, concanavalin A, or overexpression of MT-MMP-1 did not significantly enhance the level of the 60-kDa protein. Instead, an immunoreactive, proteolytically processed 43-kDa form was observed, and its appearance correlated to 72-kDa gelatinase processing activity. Thus 72-kDa gelatinase activation, while enhanced by MT-MMP-1 expression, needs additional co-operating factors.