Figure 4.

Tumor-Associated Genes Are Similarly Deregulated in CCl₄-Induced and Diethylnitrosamine-Induced TG221 Liver Tumors

(A) The tumor-associated genes Afp, Tff3, Scd2, Lpl, and Gpc3 were highly expressed in TG221 liver tumors in both cirrhotic and non-cirrhotic conditions. A clear progression in their expression level was also observed from normal livers to cirrhotic livers and CCl₄-induced or diethylnitrosamine (DEN)-induced HCC. The p values refer to mRNA expression levels in cirrhotic (CL) and HCC conditions versus those in normal livers (NL). The scale on the ordinate axis refers to mRNA expression related to that in normal livers. (B) Unsupervised hierarchical cluster analysis of gene expression to assess similarities between tumors arising in TG221 mice after DEN treatment versus those induced by CCl₄ treatment. Most TG221 DEN-derived tumors (HCC DEN-TG) were found to be carcinomas. Normal livers (NL-WT), cirrhotic livers (CL-WT), and DEN-derived tumors (HCC DEN-WT) from WT mice were also included in this analysis. The analysis was performed using a list of genes described as markers of hepatic tumor progression as well as markers of proliferating and self-renewing liver cells. HCC CCl₄ samples exhibited an expression profile that was highly similar to that of HCC DEN samples, whereas cirrhotic livers from TG221 mice (CL-TG) displayed an intermediate expression pattern between that of HCC and normal liver. Color legend is as follows: NL-WT, pink boxes; CL-WT, light blue boxes; HCC DEN-WT, blue boxes; NL-TG, red boxes; CL-TG, black boxes; HCC DEN-TG, green boxes; and HCC CCl₄-TG, gray boxes. Abbreviations are as follows: Afp, alpha fetoprotein; Scd2, stearoyl-Coenzyme A desaturase 2; Gpc3, glypican 3; Prom1, prominin 1; Lpl, lipoprotein lipase; Tff3, trefoil factor 3; Mcm2, minichromosome maintenance-deficient 2 mitotin; Met, met proto-oncogene; Yap1, yes-associated protein 1; Mst1, macrophage-stimulating 1 (hepatocyte growth factor-like); CD44, CD44 antigen; Hgf, hepatocyte growth factor; Tacstd2, tumor-associated calcium signal transducer 2; Vim, Vimentin; Il6, interleukin-6; and Bmp2, bone morphogenetic protein 2. In the image, TG221 is indicated as TG.