Sasaki N, Morisaki T, Hashizume K, Yao T, Tsuneyoshi M, Noshiro H, Nakamura K, Yamanaka T, Uchiyama A, Tanaka M, Katano M
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Clin Cancer Res. 2001 Dec;7(12):4136-42.
Activation of transcription factor nuclear factor-kappaB (NF-kappaB) 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-kappaB is constitutively activated in human gastric carcinoma tissues and, if so, to determine any correlation between NF-kappaB activity and clinicopathological features of gastric carcinoma.
NF-kappaB activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 64 gastric carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-kappaB activation.
Nuclear translocation of RelA was significantly high in tumor cells in comparison to that in adjacent normal epithelial cells (22.5 +/- 2.4% versus 8.6 +/- 1.5%, P < 0.0001). There was a significant correlation between NF-kappaB activation (nuclear translocation of RelA) and expression of urokinase-type plasminogen activator, an invasion-related factor and target of NF-kappaB in tumor cells (rho = 0.393; P = 0.0013). NF-kappaB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion of tumor cells (P = 0.0126), depth of invasion (P = 0.0539), peritoneal metastases (P = 0.0538), and tumor size (P = 0.0164).
Collectively, the data show that NF-kappaB is constitutively activated in human gastric carcinoma tissues and suggest that NF-kappaB activity is related to tumor progression due to its transcriptional regulation of invasion-related factors such as urokinase-type plasminogen activator.
转录因子核因子-κB（NF-κB）的激活已被证明在细胞增殖、凋亡、细胞因子产生和肿瘤发生中起作用。本研究的目的是确定NF-κB在人胃癌组织中是否被持续激活，如果是，则确定NF-κB活性与胃癌临床病理特征之间的任何相关性。
通过对64例胃癌患者福尔马林固定、石蜡包埋标本的免疫组织化学分析来确定NF-κB的激活情况。我们将RelA的核染色定量作为NF-κB激活的标志物。
与相邻正常上皮细胞相比，肿瘤细胞中RelA的核转位显著升高（22.5±2.4%对8.6±1.5%，P<0.0001）。NF-κB激活（RelA的核转位）与尿激酶型纤溶酶原激活物的表达之间存在显著相关性，尿激酶型纤溶酶原激活物是肿瘤细胞中的一种侵袭相关因子和NF-κB的靶点（ρ=0.393；P=0.0013）。NF-κB激活与肿瘤侵袭相关的临床病理特征相关，如肿瘤细胞的淋巴侵袭（P=0.0126）、侵袭深度（P=0.0539）、腹膜转移（P=0.0538）和肿瘤大小（P=0.0164）。
总体而言，数据表明NF-κB在人胃癌组织中被持续激活，并表明NF-κB活性因其对侵袭相关因子如尿激酶型纤溶酶原激活物的转录调控而与肿瘤进展相关。
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