Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression.

Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression.
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DOI:
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发表时间:
2004-03
影响因子:
2
通讯作者:
M. Kojima;T. Morisaki;Nobuhiko Sasaki;K. Nakano;R. Mibu;Masao Tanaka;M. Katano
M. Kojima;T. Morisaki;Nobuhiko Sasaki;K. Nakano;R. Mibu;Masao Tanaka;M. Katano
中科院分区:
医学4区
文献类型:
--
作者:
M. Kojima;T. Morisaki;Nobuhiko Sasaki;K. Nakano;R. Mibu;Masao Tanaka;M. Katano

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目的 核因子-kB (NF-kB) 是一种转录因子,参与细胞因子和酶的多个基因的诱导,这些细胞因子和酶在各种细胞类型中发挥重要的功能作用。本研究的目的是确定人类结直肠癌中 NF-kB 的激活状态及其与患者临床病理特征的相关性。材料和方法 我们通过电泳迁移率变动分析 (EMSA) 和 NF-kB p65 亚基的免疫组织化学染色,检查了 28 例切除的结直肠癌和这些标本未受累部分的结肠粘膜中 NF-kB 的激活状态。结果 EMSA 在肿瘤中显示出比在正常粘膜中更强的激活,上皮 p65 免疫染色也是如此。在进展较大的病例(T3 + T4 病例或 II 期 < 病例)中,NF-kB 激活显着增加。使用脂多糖 (LPS) 反应性结肠癌细胞的体外研究表明 NF-kB 激活与细胞增殖之间存在相关性。结论我们的研究结果表明,NF-kB 在人结直肠癌组织中持续激活,并与肿瘤进展相关。该转录因子的调节可能对这些肿瘤有治疗作用。
OBJECTIVES Nuclear factor-kB (NF-kB) is a transcription factor that participates in the induction of several genes for cytokines and enzymes that play important functional roles in various cell types. The aim of this study was to determine NF-kB activation status in human colorectal carcinoma and its correlation to the clinicopathological characteristics of patients. MATERIALS AND METHODS We examined the activation status of NF-kB in 28 resected colorectal carcinomas and in colonic mucosa from uninvolved portions of these specimens by electrophoretic mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit of NF-kB. RESULTS EMSA showed much greater activation in the tumors than in normal mucosa, as did epithelial p65 immunostaining. NF-kB activation significantly increased in the more progressed cases (T3 + T4 cases or Stage II< cases). In vitro studies using lipopolysaccharide (LPS)-responsive colon carcinoma cells suggested a correlation between NF-kB activation and cell proliferation. CONCLUSION Our findings indicated that NF-kB is constitutively activated in human colorectal carcinoma tissue and correlates with tumor progression. The regulation of this transcription factor might be therapeutically useful against these tumors.