BRG1在人腦膠質(zhì)瘤中的表達(dá)及其在體外對(duì)膠質(zhì)瘤細(xì)胞增殖、遷移和侵襲的調(diào)控.pdf

1、Background:Glial tumors are the most common type of primary brain neoplasm and constitute more than 70％ of all primary brain tumors.The most malignant histological type is the glioblastoma,less than 3％ of glioblastoma pa

2、tients are still alive at 5 years after diagnosis.Current treatment modalities for glioma patients including surgical resection,radiation therapy and chemotherapy,but most of glioblastoma patients survival time is still

3、approximately 1 year.Abnormal activation o oncogene and inactivation of anti-oncogene relate to the tumor formation of glioma.The exact mechanism of glioma is still unclear,and the lackage of accurate and effective metho

4、d for early diagnosis is the main cause to induce the high mortality.Therefore,exploration of genetic alterations closely linked with glioma formation and dissemination would be of great values in prevention,early detect

5、ion,prognostic evaluation and prolongation live time of this malignancy.
　　 The SWI/SNF chromatin remodeling complex plays important roles in cellular processes including cell differention,cell cycle control and DNA

6、repair.The studies found that aberrant expression of SWI/SNF subunits is involved in cancer development.The core subunit of the SWI/SNF complex,SNF5,has been shown to be inactivated in malignant thabdoid tumours and has

7、been defined as a tumour suppressor.However,the role of the catalytic subunit of the SWI/SNF,BRG1,is not well defined in cancer.
　　 Objectives:To investigate the role of BRG1 in glioma development,we examined the exp

8、ression of BRG1 in glioma at different stage and analysed the correlation between BRG1 expression and clinicopathological variables,and further analysed the effect of BRG1 in glioma cell growth,migration and invasion.

9、>　　 Methods:Using tissue microarray and immunohistochemistry,we evaluated BRG1 staining in 190 glioma tissues,8 normal brain tissues and 8 tumor adjacent normal brain tissues.We studied glioma cell proliferative ability

10、 with reduced BRG1 expression by small interfering RNA using CCK-8 cell proliferation assay and cell cycle analysis.Then,we studied the role of BRG1 in glioma cell migration and invasion by Transwell migration assay and

11、matrigel invasion assay.We performed westem blot to detect Cyclin Dl, Cyclin B1 and MMP-2 protein expression.At the same time,we also detected MMP-2 enzyme activity by gelatin zymography.
　　 Results:Our results showe

12、d that BRG1 expression was increased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P＜0.01).However,there is no significant difference in BRG1 staining between benign tumor and mali

13、gnant tumor (P=0.847,X2 test).We did not find any correlation between BRG1 expression and clinicopathological parameters.In addition,we found that knockdown of BRG1 in U251 and U87 glioma cell lines inhibits cell growth

14、due to G1 phase arrest by downregulating Cyclin D1 and Cyclin B1 in vitro assay.We further demonstrated that silence of BRG1 in glioma cells inhibited cell migration and invasion abilities, and down-regulation of MMP-2 e

15、xpression greatly contributed to the reduced cell invasion and migration abilities.
　　 Conclusions:Our data indicated that BRG1 expression is significantly increased in human glioma and it may be involved in the proc