肝癌形成过程中转化生长因子β1动态表达及其基因的扩增分析

Dynamic Expression of Transforming Growth Factor-β1 during the Formation of Hepatocellular Carcinoma

目的:观察肝癌(HCC)发生过程中转化生长因子(TGF)-β1及其基因的动态表达。方法:以2-乙酰氨基芴(2-FAA)喂饲雄性SD鼠诱发肝细胞癌变,以病理学方法、巢式逆转录聚合酶链反应、免疫组织化学法和酶联免疫吸附法,观察肝细胞形态学、TGF-β1 mRNA、TGF-β1胞内定位、肝组织及外周血TGF-β1的动态变化。结果:病理学证实SD鼠在喂饲2-FAA后,肝细胞出现颗粒样变性、不典型增生到HCC形成。在此过程中肝组织TGF-β1及TGF-β1 mRNA均呈梯度表达,表现为癌变组明显高于对照组、肝细胞变性组和癌前病变组(P<0.05),免疫组化显示癌变过程中TGF-β1阳性表达和胞内分布;在诱癌后的表达特征与TGF-β1 mRNA相似,肝组织和外周血中TGF-β1呈显著正相关。结论:TGF-β1参与肝细胞癌变过程,在肝癌发生早期过表达有助于肝癌早期诊断及预后判断。

Objective： To investigate the dynamic expression of TGF-β1 mRNA and protein at different stages of hepatocellular carcinoma （HCC） development. Methods： Male Sprague-Dawley （SD） tats were used as hepatoma models and were induced with 2-FAA. Morphological changes in rat livers were observed by H＆E staining. A fragment of the TGF-β1 gene was amplified by nested RT-PCR. Dynamic changes in the level of TGF-β1 protein were quantitatively analyzed by ELISA. Simultaneously, the expression and cellular distribution of TGF-β1 were detected in rat livers by immunohisto- chemistry. Results： Histological examination confirmed the rat hepatocytes progressed from granule-like degeneration to atypical hyperplasia and HCC development after induction with 2-FAA. Following this development, hepatic TGF-β1 mRNA and protein increased. The mRNA and protein levels in hepatoma tissues were significantly higher than those in normal tissues （P〈0.05）. The immunohistochemistry results indicated the positive expression and hepatocyte distribution of TGF-β1 in rat hepatoma. Similar to TGF-β1 mRNA, a trend of increasing TGF-β1 protein expression was found in precancerous to cancerous tissues during HCC development, and a positive relationship was found between the expression levels of TGF-β1 mRNA and protein. Conclusion： TGF-β1 may participate in hepatocyte carcinogenesis. The early expression of TGF-β1 during HCC development could be a useful molecular marker for early diagnosis and prognosis of HCC.