Document Detail


The regulating role of mutant IkappaBalpha in expression of TIMP-2 and MMP-9 in human glioblastoma multiform.
MedLine Citation:
PMID:  19187648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Our previous studies demonstrated that mutant IkappaBalpha (IkappaBalphaM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IkappaBalphaM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IkappaBalphaM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM. METHODS: We established the following four GBM cell lines stably expressing IkappaBalphaM by plasmid construction, gene transfection and screening for IkappaBalphaM protein expression: mutant IkappaBalpha-transfected cells (G36Delta-M), wild-type IkappaBalpha-transfected cells (G36Delta-W), empty plasmid transfected cells (G36Delta-P) and untransfected cells (G36Delta). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods. RESULTS: The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36Delta-M group at both the RNA and protein levels compared with the G36Delta-W group, G36Delta-P group and G36Delta group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36Delta-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups. CONCLUSIONS: Our findings indicate that IkappaBalphaM inhibits the activation of NF-kappaB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IkappaBalphaM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.
Authors:
Yu-hua Hu; Li-jie Yu; En-de Shao; Jian-liang Wu; Jian-wen Ji
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese medical journal     Volume:  122     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-02-03     Completed Date:  2009-05-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  205-11     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Line, Tumor
Glioblastoma / genetics,  metabolism*
Humans
I-kappa B Proteins / genetics,  physiology*
Immunohistochemistry
Matrix Metalloproteinase 2 / genetics,  metabolism*
Matrix Metalloproteinase 9 / genetics,  metabolism*
Mice
Mice, Nude
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/I-kappa B Proteins; 139874-52-5/NF-kappaB inhibitor alpha; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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