肝核转录因子-κB 在大鼠肝癌发生中的表达特征及其定量分析。

Characteristics of hepatic nuclear-transcription factor-kappa B expression and quantitative analysis in rat hepatocarcinogenesis.

机构信息

Research Center of Clinical Molecular Biology, Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2009 Oct;8(5):504-9.

PMID:19822494

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of nuclear-transcription factor-kappa B (NF-kappaB) during hepatocarcinogenesis in order to evaluate its dynamic expression and its clinical value in the development and diagnosis of HCC.

METHODS

Hepatoma models were induced by oral administration of 2-acetamidoflurene (2-FAA) to male Sprague-Dawley rats. Morphological changes were observed after hematoxylin and eosin staining. The cellular distribution of NF-kappaB expression during different stages of cancer development was investigated by immunohistochemistry, and the level of NF-kappaB expression in liver tissues was quantitatively analyzed by ELISA. The gene fragments of hepatic NF-kappaB were amplified by nested-polymerase chain reaction assay.

RESULTS

Hepatocytes showed vacuole-like degeneration during the early stages, then had a hyperplastic nodal appearance during the middle stages, and finally progressed to tubercles of cancerous nests with high differentiation. The NF-kappaB-positive material was buff-colored, fine particles localized in the nucleus, and the incidence of NF-kappaB-positive cells was 81.8% in degeneration, 83.3% in precancerous lesions, and 100% in cancerous tissues. All of these values were higher than those in controls (P<0.01). Hepatic NF-kappaB expression and hepatic NF-kappaB-mRNA were also higher during the course of HCC development (P<0.01).

CONCLUSION

The NF-kappaB signal transduction pathway is activated during the early stages of HCC development, and its abnormal expression may be associated with the occurrence of HCC.

摘要

背景

肝细胞癌（HCC）是最常见的恶性肿瘤之一。我们分析了核转录因子-κB（NF-κB）在肝癌发生过程中的表达，以评估其在 HCC 发展和诊断中的动态表达及其临床价值。

方法

通过给雄性 Sprague-Dawley 大鼠口服 2-乙酰氨基芴（2-FAA）诱导肝癌模型。苏木精和伊红染色后观察形态学变化。通过免疫组织化学法研究 NF-κB 表达在癌症发展不同阶段的细胞分布，并通过 ELISA 定量分析肝组织中 NF-κB 的表达水平。通过巢式聚合酶链反应检测肝 NF-κB 的基因片段。

结果

肝细胞在早期表现为空泡样变性，中期出现增生结节样外观，最后进展为高分化癌巢结节。NF-κB 阳性物质呈浅黄色，细小颗粒定位于细胞核内，NF-κB 阳性细胞的发生率在变性期为 81.8%，癌前病变期为 83.3%，癌组织期为 100%。所有这些值均高于对照组（P<0.01）。在 HCC 发展过程中，肝 NF-κB 表达和肝 NF-κB-mRNA 也升高（P<0.01）。