Regulation of membrane-type matrix metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate

Eur J Biochem. 1996 Jul 15;239(2):239-47. doi: 10.1111/j.1432-1033.1996.0239u.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Calcimycin / pharmacology
  • Cell Line
  • Collagenases / biosynthesis*
  • Concanavalin A / pharmacology
  • Cycloheximide / pharmacology
  • Cytokines / pharmacology*
  • DNA Primers
  • Dexamethasone / pharmacology
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblasts
  • Fibrosarcoma
  • Gelatinases / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Growth Substances / pharmacology*
  • Humans
  • Immunoblotting
  • Interleukin-1 / pharmacology
  • Lung
  • Matrix Metalloproteinase 1
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription, Genetic / drug effects*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • DNA Primers
  • Growth Substances
  • Interleukin-1
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Concanavalin A
  • Calcimycin
  • Epidermal Growth Factor
  • Dexamethasone
  • Cycloheximide
  • Collagenases
  • Gelatinases
  • Matrix Metalloproteinase 1
  • Tetradecanoylphorbol Acetate

Associated data

  • GENBANK/X90925