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目的:探讨Wnt/β-catenin信号转导通路与肿瘤发生的关系,为肝癌的防治提供新的思路。方法:选取Wnt/β-catenin信号转导通路中上下游关键因子wnt1、β-catenin、APC、cyclinD1以及c-myc等,应用RT-PCR法观察它们在正常肝脏,不典型增生肝脏和肝癌组织中的转录水平。用免疫组化染色法研究β-catenin、APC和cyclinD1等3个因子有无表达。结果:在正常肝脏中,用RT-PCR未检测到wnt1、cyc-linD1以及c-myc的mRNA转录,免疫组化染色也只观察到β-catenin在细胞膜处有比较弱的表达。诱癌14周后,在发生不典型增生的肝组织中,检测到β-catenin、APC和cyclinD13个基因的转录。通过免疫组化染色也观察到β-catenin蛋白在胞质中的积累,APC和cyclinD1在部分细胞中出现表达。诱癌16周后,在肝癌组织中,除wnt1mRNA外,其他几个因子的mRNA都有转录,免疫组化也印证了上述各个发生转录的因子在蛋白水平都有不同程度的表达。结论:Wnt/β-catenin信号转导通路在大鼠的肝癌形成过程中被激活,其可能是实验性肝癌发生的原因之一。
Objective: To investigate the relationship between Wnt / β-catenin signal transduction pathways and tumorigenesis and to provide new ideas for the prevention and treatment of liver cancer. Methods: Wnt1, β-catenin, APC, cyclinD1 and c-myc were detected by RT-PCR in the normal liver, atypical hyperplasia liver and hepatocellular carcinoma In the transcription level. The expression of β-catenin, APC and cyclinD1 were detected by immunohistochemistry. Results: In normal liver, no mRNA transcripts of wnt1, cyc-linD1 and c-myc were detected by RT-PCR. Only weak expression of β-catenin in the cell membrane was observed by immunohistochemistry. After 14 weeks of inducing cancer, 13 genes of β-catenin, APC and cyclinD were detected in atypical hyperplasia liver tissues. The accumulation of β-catenin protein in the cytoplasm was also observed by immunohistochemical staining. APC and cyclinD1 were expressed in some cells. Sixteen weeks after induction of cancer, in addition to wnt1 mRNA, several mRNAs of other factors were transcribed in HCC tissues. Immunohistochemistry also confirmed that the transcription factors mentioned above all expressed at different protein levels. Conclusion: The Wnt / β-catenin signal transduction pathway is activated in the process of hepatocarcinogenesis in rats, which may be one of the reasons for the development of experimental liver cancer.