Scuric Z, Stain S C, Anderson W F, Hwang J J
Gene Therapy Laboratories, University of Southern California School of Medicine, Los Angeles 90033, USA.
Hepatology. 1998 Apr;27(4):943-50. doi: 10.1002/hep.510270408.
The multistep process of liver carcinogenesis involves various genetic and phenotypic alterations. To identify genes whose expression is increased during hepatocarcinogenesis, differential-display polymerase chain reaction (DD-PCR) was used to examine differences in the mRNA composition of hepatocellular carcinoma (HCC) versus normal liver (nontumor) tissues. This approach identified 67 cDNAs that were preferentially expressed in HCC tissue. When these cDNAs were analyzed by reverse-Northern analysis, five were reproducibly expressed at high levels in HCC. Interestingly, Northern blot analysis revealed that one of the genes showed significantly increased mRNA levels in all five tested tumor samples, while its mRNA level in the nontumor samples was minimal. BLAST analysis revealed that this gene has high sequence identity with the genes from aldo-keto reductase family of proteins including the mouse fibroblast growth factor-induced gene (FR-1) (80% identity), mouse vas deferens protein (MVDP) (76%), and human aldose reductase (AR) (62%). Expression of this novel AR-related protein in all five tested HCCs suggests that this protein may play an important role in liver carcinogenesis.
肝癌发生的多步骤过程涉及多种基因和表型改变。为了鉴定在肝癌发生过程中表达增加的基因，采用差异显示聚合酶链反应（DD-PCR）来检测肝细胞癌（HCC）与正常肝脏（非肿瘤）组织mRNA组成的差异。该方法鉴定出67个在HCC组织中优先表达的cDNA。当通过反向Northern分析对这些cDNA进行分析时，有5个在HCC中可重复地高水平表达。有趣的是，Northern印迹分析显示，在所有5个测试的肿瘤样本中，其中一个基因的mRNA水平显著增加，而其在非肿瘤样本中的mRNA水平极低。BLAST分析表明，该基因与醛糖酮还原酶蛋白家族的基因具有高度序列同一性，包括小鼠成纤维细胞生长因子诱导基因（FR-1）（同一性为80%）、小鼠输精管蛋白（MVDP）（76%）和人醛糖还原酶（AR）（62%）。这种新型AR相关蛋白在所有5个测试的HCC中的表达表明，该蛋白可能在肝癌发生中起重要作用。
