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

Liver carcinogenesis is a multistep process involving various genetic alter ations. cDNA microarray containing 1,080 elements (930 unique genes) was us ed to comprehensively analyze the genetic alterations in hepatoma cell line s, and clustering analysis was used to analyze the relatedness of the gene- expression profiles. Among 7 hepatoma cell lines analyzed, 5 alpha -fetopro tein (AFP)-producing hepatoma cell lines (HepG2, Huh7, Hep3B, PLC/PRF/5, an d Huh6) were shown to have common gene-expression profiles compared with th ose of AFP-negative hepatoma cell lines (HLE and SK-Hep1) and cancer cell l ines of nonhepatocyte origin (HeLa and KMBC). Furthermore, HepG2, Huh7, and Hep3B had higher expressions of AFP and shared a common gene-expression pr ofile even when compared with other AFP-producing cells. Analysis of the ge nes with a common expression profile among these 3 AFP-positive cells revea led 254 genes across various categories. We found that 18 of these genes co nsistently showed altered levels of expression (more than 3-fold changes) i n the 3 AFP-producing hepatoma cell lines (11 up-regulated and 7 down-regul ated). 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 di stinct 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.