Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma.
Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma.
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发表时间：
2001-04
期刊：
影响因子：
11.2
通讯作者：
Lian Xu;Lijian Hui;Shaohui Wang;Jialei Gong;Ying Jin;Yanping Wang;Yuan Ji;Xin Wu;Zheguang Han;Gengxi Hu
中科院分区：
文献类型：
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作者：
Lian Xu;Lijian Hui;Shaohui Wang;Jialei Gong;Ying Jin;Yanping Wang;Yuan Ji;Xin Wu;Zheguang Han;Gengxi Hu
通过使用包含14000个cDNA簇的cDNA阵列，我们研究了来自同一患者的配对临床肝细胞癌（HCC）样本和远端非肿瘤肝组织的表达谱。尽管临床样本之间存在显著的异质性，但在已鉴定的50%的癌症样本中，有72个基因（包括30个新基因）下调，84个基因（包括48个新基因）上调。通过Northern blot和反转录PCR证实了4个随机选择的基因表达水平的改变。值得注意的是，先前研究的38个肝癌（HCC）下调基因中有21个被一组肝脏富集转录因子（LETFs）调控，而先前研究的36个HCC上调基因中有12个参与蛋白质翻译。对cDNA阵列数据的复查进一步显示，在至少一部分HCC样本中，大多数已知由letf调节的基因都是下调的。在letf中，CCAAT/增强子结合蛋白(C/EBP) α在肿瘤中表达下调，而肝细胞核因子1 （HNF-1）、hnf -3 β、hnf -4 α和hnf -4 γ表达上调。因此，表达谱表明HCC涉及多种调控途径，特别是与letf相关的调控途径。
By using a cDNA array representing 14,000 cDNA clusters, we studied the expression profiles in paired clinical hepatocellular carcinoma (HCC) samples and the distal nontumorous liver tissues from the same patients. Despite the significant heterogeneity among the clinical samples, 72 genes (including 30 novel genes) were down-regulated and 84 genes (including 48 novel genes) were up-regulated in >50% of the cancer samples that were identified. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription PCR in all of 4 randomly selected genes. It was conspicuous that 21 of 38 hepatocarcinoma (HCC) down-regulated genes studied previously were reportedly regulated by a group of liver-enriched transcription factors (LETFs), and 12 of 36 HCC up-regulated genes studied previously were involved in protein translation. Reexamination of the cDNA array data further revealed that most of the genes known to be regulated by LETFs were down-regulated in at least a portion of the HCC samples. Among the LETFs, the expression level of CCAAT/enhancer-binding protein (C/EBP) alpha was down-regulated in cancer, whereas hepatocyte nuclear factor 1 (HNF-1), HNF-3beta, HNF-4alpha, and HNF-4gamma were up-regulated. The expression profiling thus suggested multiple regulatory pathways involved in HCC, especially that related to LETFs.