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核因子-κB调节人结肠直肠癌组织中环氧合酶-2的表达和细胞增殖。

Nuclear factor-kappa B regulates cyclooxygenase-2 expression and cell proliferation in human colorectal carcinoma tissue.

作者信息

Yu Liang-Liang, Yu Hong-Gang, Yu Jie-Ping, Luo He-Sheng

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China.

出版信息

Eksp Onkol. 2004 Mar;26(1):40-7.

Abstract

OBJECTIVE

Activation of transcription factor nuclear factor-kappa B (NF-kappa B) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappa B is constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-kappa B in colorectal tumorigenesis, furthermore, to determine the association of RelA expression with the expression of cyclooxygenase-2 (COX-2) and tumor cell proliferation.

METHODS

Paraffin sections of the normal epithelial, adenomatous and adenocarcinoma tissue were analysed immunohistochemically for RelA, COX-2, Ki-67 protein expression. EMSA (electrophoretic mobility shift assay) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The expression of COX-2 mRNA was determined by RT-PCR (reverse transcription polymerase chain reaction) analysis.

RESULTS

Activation of NF-kappa B was significantly higher in adenocarcinoma tissue in comparison to that in adenomatous and normal epithelial tissue. The colon tumor cell proliferation, mRNA expression and protein level of COX-2 were significantly increased in the transition from normal to tumor tissue.

CONCLUSION

Our results suggest that NF-kappa B may promote proliferation via enhancing the expression of COX-2, and the increased expression of RelA/nuclear factor-kappa B plays an important role in the pathogenesis of colorectal carcinoma.

摘要

目的

转录因子核因子-κB(NF-κB)的激活已被证明在细胞增殖、凋亡、细胞因子产生及肿瘤发生中起作用。本研究的目的是确定NF-κB在人结肠肿瘤组织中是否组成性激活,若如此,确定NF-κB在结肠肿瘤发生中的作用,此外,确定RelA表达与环氧化酶-2(COX-2)表达及肿瘤细胞增殖的相关性。

方法

对正常上皮、腺瘤及腺癌组织的石蜡切片进行免疫组织化学分析,检测RelA、COX-2、Ki-67蛋白表达。采用电泳迁移率变动分析(EMSA)证实结肠肿瘤组织中RelA核转位增加。通过逆转录聚合酶链反应(RT-PCR)分析确定COX-2 mRNA的表达。

结果

与腺瘤及正常上皮组织相比,腺癌组织中NF-κB的激活显著更高。从正常组织向肿瘤组织转变过程中,结肠肿瘤细胞增殖、COX-2的mRNA表达及蛋白水平均显著增加。

结论

我们的结果表明,NF-κB可能通过增强COX-2的表达促进增殖,RelA/核因子-κB表达增加在结直肠癌发病机制中起重要作用。

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