PMID- 11426939
OWN - NLM
STAT- MEDLINE
DCOM- 20011214
LR  - 20081121
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 267
IP  - 2
DP  - 2001 Jul 15
TI  - CD40L induces matrix-metalloproteinase-9 but not tissue inhibitor of 
      metalloproteinases-1 in cervical carcinoma cells: imbalance between NF-kappaB and 
      STAT3 activation.
PG  - 205-15
AB  - Matrix-metalloproteinases (MMPs) are essentially required for tumor cell invasion 
      and metastasis. Production of precursor enzymes is regulated on transcriptional 
      level, while activation of the pro-enzymes is tightly controlled by 
      posttranscriptional mechanisms. The enzyme activity can be blocked by specific 
      tissue inhibitors of MMPs (TIMPs). In cervical carcinomas strong up-regulation of 
      the type IV collagenase MMP-9 had been demonstrated. We show that activation of 
      CD40, a receptor highly expressed on cervical carcinomas, induces MMP-9 in 
      cervical carcinoma cells, whereas TIMP-1 production inhibiting MMP-9 activity was 
      not affected. This gene induction pattern corresponded to the differential 
      activation of the transcription factor nuclear factor kappaB (NF-kappaB) 
      regulating MMP-9, but not signal transducer and activator of transcription 3 
      (STAT3), which is involved in TIMP-1 gene regulation. Transient expression of the 
      CD40-inducible NF-kappaB subunit p65 was sufficient for MMP-9 induction. Agents 
      that suppressed CD40-mediated NF-kappaB activation also reduced MMP-9 induction, 
      further supporting an important role of NF-kappaB in CD40-mediated MMP-9 
      induction. Our data suggest that CD40 expression in carcinoma cells might convert 
      a CD40L-dependent immunological defense signal into a tumor-promoting signal. 
      Selective CD40-mediated signaling through NF-kappaB but not STAT3 correlates to a 
      shift of the balance between MMP-9 and TIMP-1 toward the protease.
CI  - Copyright 2001 Academic Press.
FAU - Smola-Hess, S
AU  - Smola-Hess S
AD  - Institute of Virology, University of Cologne, Furst-Puckler-Str. 56, Cologne, 
      50935, Germany. s.hess@uni-koeln.de
FAU - Schnitzler, R
AU  - Schnitzler R
FAU - Hadaschik, D
AU  - Hadaschik D
FAU - Smola, H
AU  - Smola H
FAU - Mauch, C
AU  - Mauch C
FAU - Krieg, T
AU  - Krieg T
FAU - Pfister, H
AU  - Pfister H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Organic Chemicals)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Sulfones)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Trans-Activators)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - CD40 Ligand/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Matrix Metalloproteinase 9/genetics/*metabolism
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - *Nitriles
MH  - *Organic Chemicals
MH  - Protease Inhibitors/metabolism
MH  - Protein Subunits
MH  - STAT3 Transcription Factor
MH  - *Sulfones
MH  - Tissue Inhibitor of Metalloproteinases/genetics/*metabolism
MH  - Trans-Activators/*metabolism
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/genetics/*metabolism
EDAT- 2001/06/28 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/06/28 10:00
PHST- 2001/06/28 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/06/28 10:00 [entrez]
AID - S0014-4827(01)95256-5 [pii]
AID - 10.1006/excr.2001.5256 [doi]
PST - ppublish
SO  - Exp Cell Res. 2001 Jul 15;267(2):205-15. doi: 10.1006/excr.2001.5256.