MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors

J Cell Mol Med. Apr-Jun 2006;10(2):499-510. doi: 10.1111/j.1582-4934.2006.tb00415.x.


The goal of our study was to analyse the prognostic values for some matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in breast cancer. We evaluated the activity and the expression levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in malignant versus benign fresh breast tumor extracts. For this purpose, gelatinzymography, immunoblotting and ELISA were used to analyse the activity and expression of MMPs and TIMPs. We found that MMP-9 expression level and activity are increased in malignant tumors. In addition, MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio values obtained by us were significantly different in malignant tumors compared to benign tumors. We suggest that the abnormal MMP-9/TIMP-1 balance plays a role in the configuration of breast invasive carcinoma of no special type and also in tumor growth, while altered MMP-2/TIMP-2 ratio value could be associated with lymph node invasion and used as a prognostic marker in correlation with Nottingham Prognostic Index. Finally, we showed that in malignant tumors high expression of estrogen receptors is associated with enhanced activity of MMP-2 and increased bcl- 2 levels, while high expression of progesterone receptors is correlated with low TIMP-1 protein levels.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / pharmacology*
  • Matrix Metalloproteinase 9 / pharmacology*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tissue Inhibitor of Metalloproteinase-1 / antagonists & inhibitors*
  • Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors*
  • Tumor Burden
  • Tumor Cells, Cultured


  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9