The regulating role of mutant IKBα in expression of TIMP-2 and MMP-9 in human glioblastoma multiform

作     者：HU Yu-hua YU Li-Jie SHAO En-de WU Jian-liang JI Jian-wen 

作者机构：Department of Neurosurgery Second Hospital of Hebei Medical University Shijiazhuang Hebei 050000 China Department of Pathology Stomatological Hospital of Hebei Medical University Shijiazhuang Hebei 050000 China Department of Neurosurgery Langfang People's Hospital Langfang Hebei 065000 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2009年第122卷第2期

页      面：205-211页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：nuclear factor-KB mutant-type IKBα metalloproteinases extracellular matrix glioma 

摘      要：Background Our previous studies demonstrated that mutant IKBα （IKBαM） inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform （GBM）. However, the specific mechanism by which IKBaM 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 IKBαM 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 IKBaM by plasmid construction, gene transfection and screening for IKBαM protein expression： mutant IKBa-transfected cells （G36A-M）, wild-type IKBa-transfected cells （G36A-W）, empty plasmid transfected cells （G36A-P） and untransfected cells （G36A）. 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 G36A-M group at both the RNA and protein levels compared with the G36A-W group, G36A-P group and G36A group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36A-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 IKBaM inhibits the activation of NF-KB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IKBαM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues. Chin Med J 2009; 122（2）：205-211