Aberrant Expression of the p53-Inducible Antiproliferative Gene BTG2 in Hepatocellular Carcinoma is Associated with Overexpression of the Cell Cycle-Related Proteins
Aberrant Expression of the p53-Inducible Antiproliferative Gene BTG2 in Hepatocellular Carcinoma is Associated with Overexpression of the Cell Cycle-Related Proteins
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DOI：
10.1007/s12013-011-9164-x
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发表时间：
2011-02
影响因子：
2.6
通讯作者：
Zhimin Zhang;Chuan Chen;Ge Wang;Zhi-xiang Yang;Jinlu San;Jijun Zheng;Qiong Li;Xi-zhong Luo;Qing Hu;Zeng-peng Li;Dong Wang
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文献类型：
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作者：
Zhimin Zhang;Chuan Chen;Ge Wang;Zhi-xiang Yang;Jinlu San;Jijun Zheng;Qiong Li;Xi-zhong Luo;Qing Hu;Zeng-peng Li;Dong Wang
我们之前报道过BTG2的异常表达与肝细胞癌（HCC）的发生/发展有关。本研究的目的是比较BTG2与p53、cyclin D1、cyclin e在HCC中的表达。为此，我们建立了修饰的二乙基亚硝胺（DEN）诱导的原发性HCC大鼠模型。分别用western blot和RT-PCR/northern blot检测靶蛋白和mrna。采用western blot检测大鼠肝脏BTG2等蛋白的表达，采用高通量组织芯片（TMA）和原位杂交（ISH）检测HCC/正常组织中BTG2 mRNA的表达。BTG2 mRNA/蛋白在胎肝、7701和LO2细胞系中表达升高，而在HepG2细胞中表达降低。BTG2/p53在DEN治疗后早期表达，5周时达到峰值，随后逐渐降低。Cyclin-D1/Cyclin-E的表达随肿瘤进展显著升高。BTG2 mRNA通过ISH在71.19%的HCC中表达，并与分化相关。BTG2 mrna阴性组织中p53/cyclin D1/cyclin E的表达分别为82.35% /94.12/76.47%。32.2% (19/59) HCC组织中BTG2蛋白表达缺失，且mRNA/蛋白表达量与肿瘤分级增加呈显著相关（P< 0.05）。总之，BTG2表达在HCC中普遍受损，这可能是肝癌发生过程中cyclin-D1/cyclin-E表达失调的一个因素。
We previously reported that the abnormal BTG2 expression was related to genesis/development of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the BTG2 expression in HCC compared with p53, cyclin D1, and cyclin E. For this purpose, modified diethylnitrosamine (DEN)-induced primary HCC rat model was established. Target proteins and mRNAs were measured by western blot and RT-PCR/northern blot, respectively. In rat liver, expression of BTG2 and other proteins was determined by western blot, and BTG2 mRNA in HCC/normal tissues was detected by high-flux tissue microarray (TMA) and in situ hybridization (ISH). BTG2 mRNA/protein expression was increased in fetal liver, 7701, and LO2 cell lines but decreased in HepG2 cells. BTG2/p53 were expressed early after DEN treatment, peaked at 5 weeks and decreased gradually thereafter. Cyclin-D1/Cyclin-E expression increased significantly with the tumor progression. BTG2 mRNA was expressed in 71.19% HCC by ISH and correlated with differentiation. Expression of p53/cyclin D1/cyclin E was positive in 82.35/94.12/76.47% BTG2 mRNA-negative tissues, respectively. BTG2 protein expression was lost in 32.2% (19/59) HCC tissues, and the mRNA/protein expression correlated significantly with the increasing tumor grade (P< 0.05). In conclusion, BTG2 expression is commonly impaired in HCC which may be a factor involved in deregulation of cyclin-D1/cyclin-E expression during hepatocarcinogenesis.