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- β 1 during the Formation of Hepatocellular Carcinoma

  • 摘要: 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。

     

    Abstract: Objective: To investigate the dynamic expression of TGF- β 1 mRNA and protein at different stages of hepatocellular carcinoma (HCC) development. Methods: Male Sprague- Dawley (SD)rats 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- β 1 protein were quantitatively analyzed by ELISA. Simultaneously, the expression and cellular distribution of TGF- β 1 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- β 1 mRNA and protein increased. The mRNA and protein levels in hep-atoma tissues were significantly higher than those in normal tissues (P<0.05). The immunohistochem-istry results indicated the positive expression and hepatocyte distribution of TGF- β 1 in rat hepatoma.Similar to TGF- β 1 mRNA, a trend of increasing TGF- β 1 protein expression was found in precancerous to cancerous tissues during HCC development, and a positive relationship was found between the expression levels of TGF- β 1 mRNA and protein. Conclusion: TGF- β 1 may participate in hepatocyte carcinogenesis. The early expression of TGF- β 1 during HCC development could be a useful molecular marker for early diagnosis and prognosis of HCC.

     

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