α-Fetoprotein-producing hepatoma cell lines share common expression profiles of genes in various categories demonstrated by cDNA microarray analysis

α-Fetoprotein-producing hepatoma cell lines share common expression profiles of genes in various categories demonstrated by cDNA microarray analysis
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DOI:
10.1053/jhep.2001.22500
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发表时间:
2001-03-01
期刊:
影响因子:
13.5
通讯作者:
Kobayashi, K
Kobayashi, K
中科院分区:
医学1区
文献类型:
--
作者:
Kawai, HF;Kaneko, S;Kobayashi, K

文献摘要

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肝癌的发生是一个多步骤的过程,涉及各种遗传改变。利用包含1,080个元件(930个独特基因)的cDNA微阵列对肝癌细胞系的遗传改变进行综合分析,并采用聚类分析对基因表达谱的相关性进行分析。在分析的7个肝癌细胞系中,5个产生甲胎蛋白(AFP)的肝癌细胞系(HepG 2、Huh 7、Hep 3B、PLC/PRF/5和Huh 6)与AFP阴性肝癌细胞系(HLE和SK-Hep 1)和非肝细胞来源的癌细胞系(HeLa和KMBC)相比具有共同的基因表达谱。此外,HepG 2,Huh 7和Hep 3B具有更高的AFP表达,即使与其他AFP产生细胞相比,也具有共同的基因表达谱。对这3种AFP阳性细胞中具有共同表达谱的基因进行分析,发现不同类别的254个基因。我们发现,这些基因中的18个在3个产生AFP的肝癌细胞系中(11个上调,7个下调)始终显示出表达水平的改变(超过3倍的变化)。在这18个基因中,包括AFP在内的5个基因先前被报道与HCC有关,6个基因仅与其他类型的癌症有关。我们的研究表明,产生AFP的肝癌细胞系共享不同类别的基因表达谱。了解这种特定的基因表达谱与AFP阳性和AFP阴性肝细胞癌(HCC)的因果关系可能有助于在未来更合理的治疗。
Liver carcinogenesis is a multistep process involving various genetic alterations. cDNA microarray containing 1,080 elements (930 unique genes) was used to comprehensively analyze the genetic alterations in hepatoma cell lines, and clustering analysis was used to analyze the relatedness of the gene-expression profiles. Among 7 hepatoma cell lines analyzed, 5 alpha -fetoprotein (AFP)-producing hepatoma cell lines (HepG2, Huh7, Hep3B, PLC/PRF/5, and Huh6) were shown to have common gene-expression profiles compared with those of AFP-negative hepatoma cell lines (HLE and SK-Hep1) and cancer cell lines of nonhepatocyte origin (HeLa and KMBC). Furthermore, HepG2, Huh7, and Hep3B had higher expressions of AFP and shared a common gene-expression profile even when compared with other AFP-producing cells. Analysis of the genes with a common expression profile among these 3 AFP-positive cells revealed 254 genes across various categories. We found that 18 of these genes consistently showed altered levels of expression (more than 3-fold changes) in the 3 AFP-producing hepatoma cell lines (11 up-regulated and 7 down-regulated). In these 18 genes, 5 genes, including that for AFP, were previously reported to be involved in HCC and 6 genes involved only in other types of cancer. Our study showed that AFP-producing hepatoma cell lines shared a distinct expression profile of genes in various categories. An understanding of a causal relationship of this particular expression profile of genes to AFP-positive and AFP-negative hepatocellular carcinoma (HCC) may contribute to more rational therapy in future.