Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma

Cancer Res. 1996 Mar 1;56(5):944-9.

Abstract

A new member of the matrix metalloproteinase (MMP) family of enzymes has been cloned from a human breast carcinoma cDNA library. The isolated cDNA contains an open reading frame 1554 bp long, encoding a polypeptide of 518 amino acids. The predicted amino acid sequence displays a similar domain organization as the remaining MMPs, including a prodomain with the activation locus, the zinc-binding site, and the hemopexin domain. In addition, it contains a C-terminal extension, rich in hydrophobic residues and similar in size to those present in the different membrane-type MMPs (MT-MMPs) identified to date. On the basis of these structural characteristics, this novel MMP has been tentatively called MT4-MMP, because it represents the fourth member of this subclass of MMPs characterized mainly by the occurrence of putative transmembrane domain in their amino acid sequences. MT4-MMP also contains a nine-residue insertion between the propeptide and the catalytic domain, which is a common feature of MT-MMPs and stromelysin-3. This amino acid sequence insertion ends with the consensus sequence R-X-R/K-R, which seems to be essential in the activation of these proteinases by furin. Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues revealed that the MT4-MMP gene (MMP-17) is expressed mainly in the brain, leukocytes, the colon, the ovary, and the testis. The expression of MT4-MMP in leukocytes together with its putative membrane localization suggest that this enzyme could be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators such as tumor necrosis factor-alpha. In addition, MT4-MMP transcripts were detected in all breast carcinomas, as well as in all breast cancer cell lines analyzed in the present work. On the basis of these expression data in breast tumors, a potential role for human MT4-MMP in the tumoral process is also suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Carcinoma / enzymology*
  • Carcinoma / genetics
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • Extracellular Matrix / enzymology
  • Female
  • Humans
  • Matrix Metalloproteinases*
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / isolation & purification
  • Molecular Sequence Data
  • Sequence Alignment

Substances

  • MMP17 protein, human
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases

Associated data

  • GENBANK/X89576