| 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 |
Related Documents
:
|
17307908 - Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteina... 3024708 - Half-life of synovial cell collagenase mrna is modulated by phorbol myristate acetate b... 16569638 - Redox-dependent matrix metalloproteinase-1 expression is regulated by jnk through ets a... 9796998 - Expression of the membrane-type 3 matrix metalloproteinase (mt3-mmp) in human brain tis... 17307908 - Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteina... 15273748 - Trans-splicing repair of cd40 ligand deficiency results in naturally regulated correcti... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephre...
Next Document: Effects of prior freezing or drying on the swelling behaviour of the bovine cornea.