Chen Yuan-neng, Cao Ji, Su Jian-jia, Li Yuan
Department of Gastroenterology, Affiliated First Hospital of Guangxi Medical University, Nanning 530021, China.
Zhonghua Gan Zang Bing Za Zhi. 2005 Oct;13(10):763-7.
To study the differential expression of genes in signal transduction pathway (STP) during the hepatocarcinogenesis in tree shrews induced by AFB1 and/or HBV and to elucidate the molecular mechanism of hepatocellular carcinoma (HCC) development.
Adult tree shrews were divided into three groups: Group A was fed AFB1 only, Group B was infected firstly with HBV then fed AFB1 as in Group A, Group C served as the normal control. Liver biopsies were obtained at the 30th, 60th and 90th week of the experiment or until HCC occurred and the animals were sacrificed. Tree shrew-specific cDNA microarray was applied for detecting the differential expression of corresponding genes in each group at different time points during the experiment, and real time RT PCR was applied to verify the results of the cDNA microarray.
Genes of IGF-II, C-rel, and NF-kappaB2 were differentially expressed between para-cancerous tissues and HCC tissues in both group A and group B, and the differential expression of bcl-2, cyclin A and CNTF was only seen in group B. Between the experimental groups A and B and the control group C, there were differential expressions of CNTF and cyclin A in the early 30th week and middle 60th week stage of hepatocarcinogenesis in tree shrews. Real time RT PCR results showed that the expression level of IGF-II and C-Rel in group A and of IGF-II in group B in HCC tissues were significantly lower than that in the adjacent non-cancerous tissues and in the biopsies taken at the 30th and 60th week of the experiment. Nevertheless, there were no significant differences between the para-cancerous tissues and the cancer tissues at the 30th and 60th week. These results were consistent with the cDNA microarray assay. The expression levels of C-Rel and CNTF in group B were not obviously altered in the para-cancerous tissues, HCC and at the 60th week, but they were significantly lower in these tissues than that in the tissues at the 30th week. In group A, the expression levels of CNTF in adjacent liver and HCC tissues were higher than that in para-cancerous lesions, but the difference did not reach a statistically significant level. In group C, the expression level of IGF-II, C-Rel and CNTF at different stages showed no significant differences, which was consistent with the cDNA microarray results.
To apply the tree shrew-specific cDNA microarray to detect the differential expression of genes related to signal transduction pathway during tree shrew hepatocarcinogenesis could be a valuable utility for further comprehending the mechanism of HCC. IGF-II, NF-kappaB2, C-rel, Bcl-2, and cyclin A. CNTF may be involved in the occurrence and progress of HCC in tree shrews.
研究黄曲霉毒素B1（AFB1）和/或乙肝病毒（HBV）诱导树鼩肝癌发生过程中信号转导通路（STP）相关基因的差异表达，阐明肝细胞癌（HCC）发生发展的分子机制。
将成年树鼩分为三组：A组仅给予AFB1；B组先感染HBV，再如A组一样给予AFB1；C组作为正常对照。在实验第30、60和90周或直至发生HCC处死动物，获取肝脏活检组织。应用树鼩特异性cDNA微阵列检测实验过程中不同时间点各组相应基因的差异表达，并采用实时RT-PCR验证cDNA微阵列结果。
A组和B组癌旁组织与HCC组织中IGF-II、C-rel和NF-κB2基因均有差异表达，bcl-2、细胞周期蛋白A和CNTF的差异表达仅见于B组。在树鼩肝癌发生的第30周早期和第60周中期，实验组A、B与对照组C之间，CNTF和细胞周期蛋白A存在差异表达。实时RT-PCR结果显示，A组HCC组织中IGF-II和C-Rel以及B组HCC组织中IGF-II的表达水平显著低于相邻非癌组织及实验第30和60周时获取的活检组织。然而，第30和60周时癌旁组织与癌组织之间无显著差异。这些结果与cDNA微阵列检测结果一致。B组癌旁组织、HCC组织及第60周时C-Rel和CNTF的表达水平无明显改变，但这些组织中的表达水平显著低于第30周时的组织。在A组中，相邻肝脏和HCC组织中CNTF的表达水平高于癌旁病变组织，但差异未达到统计学显著水平。在C组中，不同阶段IGF-II、C-Rel和CNTF的表达水平无显著差异，这与cDNA微阵列结果一致。
应用树鼩特异性cDNA微阵列检测树鼩肝癌发生过程中信号转导通路相关基因的差异表达，对于进一步理解HCC的发生机制具有重要价值。IGF-II、NF-κB2、C-rel、Bcl-2、细胞周期蛋白A和CNTF可能参与树鼩HCC发生发展过程。
