PMID- 19144199
OWN - NLM
STAT- MEDLINE
DCOM- 20090204
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 9
DP  - 2009 Jan 14
TI  - Correlation between MMPs and their inhibitors in breast cancer tumor tissue 
      specimens and in cell lines with different metastatic potential.
PG  - 20
LID - 10.1186/1471-2407-9-20 [doi]
AB  - BACKGROUND: The metastatic disease rather than the primary tumor itself is 
      responsible for death in most solid tumors, including breast cancer. The role of 
      matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and 
      Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in the 
      metastatic process has previously been established. However, in all published 
      studies only a limited number of MMPs/MMP inhibitors was analyzed in a limited 
      number of cell lines. Here, we propose a more comprehensive approach by analyzing 
      the expression levels of several MMPs (MMP-2, MMP-9 and MMP-14) and MMP 
      inhibitors (TIMP-1, TIMP-2 and RECK) in different models (five human breast 
      cancer cell lines, 72 primary breast tumors and 30 adjacent normal tissues). 
      METHODS: We analyzed the expression levels of MMP-2, MMP-9 and MMP-14 and their 
      inhibitors (TIMP-1, TIMP-2 and RECK) by quantitative RT-PCR (qRT-PCR) in five 
      human breast cancer cell lines presenting increased invasiveness and metastatic 
      potential, 72 primary breast tumors and 30 adjacent normal tissues. Moreover, the 
      role of cell-extracellular matrix elements interactions in the regulation of 
      expression and activity of MMPs and their inhibitors was analyzed by culturing 
      these cell lines on plastic or on artificial ECM (Matrigel). RESULTS: The results 
      demonstrated that MMPs mRNA expression levels displayed a positive and 
      statistically significant correlation with the transcriptional expression levels 
      of their inhibitors both in the cell line models and in the tumor tissue samples. 
      Furthermore, the expression of all MMP inhibitors was modulated by cell-Matrigel 
      contact only in highly invasive and metastatic cell lines. The enzyme/inhibitor 
      balance at the transcriptional level significantly favors the enzyme which is 
      more evident in tumor than in adjacent non-tumor tissue samples. CONCLUSION: Our 
      results suggest that the expression of MMPs and their inhibitors, at least at the 
      transcriptional level, might be regulated by common factors and signaling 
      pathways. Therefore, the multi-factorial analysis of these molecules could 
      provide new and independent prognostic information contributing to the 
      determination of more adequate therapy strategies for each patient.
FAU - Figueira, Rita C S
AU  - Figueira RC
AD  - Department of Biochemistry, Chemistry Institute, University of Sao Paulo, Sao 
      Paulo, Brazil. ritabio@iq.usp.br
FAU - Gomes, Luciana R
AU  - Gomes LR
FAU - Neto, Joao S
AU  - Neto JS
FAU - Silva, Fabricio C
AU  - Silva FC
FAU - Silva, Ismael D C G
AU  - Silva ID
FAU - Sogayar, Mari C
AU  - Sogayar MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090114
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RECK protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
SB  - IM
MH  - Breast Neoplasms/enzymology/genetics/*metabolism/*pathology
MH  - Cell Line, Tumor
MH  - GPI-Linked Proteins
MH  - Humans
MH  - Matrix Metalloproteinase 14/biosynthesis/genetics
MH  - Matrix Metalloproteinase 2/biosynthesis/genetics
MH  - Matrix Metalloproteinase 9/biosynthesis/genetics
MH  - Matrix Metalloproteinases/*biosynthesis/genetics
MH  - Membrane Glycoproteins/biosynthesis/genetics
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinases/*biosynthesis/genetics
PMC - PMC2631003
EDAT- 2009/01/16 09:00
MHDA- 2009/02/05 09:00
PMCR- 2009/01/14
CRDT- 2009/01/16 09:00
PHST- 2008/09/02 00:00 [received]
PHST- 2009/01/14 00:00 [accepted]
PHST- 2009/01/16 09:00 [entrez]
PHST- 2009/01/16 09:00 [pubmed]
PHST- 2009/02/05 09:00 [medline]
PHST- 2009/01/14 00:00 [pmc-release]
AID - 1471-2407-9-20 [pii]
AID - 10.1186/1471-2407-9-20 [doi]
PST - epublish
SO  - BMC Cancer. 2009 Jan 14;9:20. doi: 10.1186/1471-2407-9-20.