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Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

Chen X, Yamamoto M, Fujii K, Nagahama Y, Ooshio T, Xin B, Okada Y, Furukawa H, Nishikawa Y - Cancer Sci. (2015)

Bottom Line: We identified tumor-associated genes that were expressed differentially in the cirrhotic CCl4 model (H19, Igf2, Cbr3, and Krt20) and the non-cirrhotic DEN model (Tff3, Akr1c18, Gpc3, Afp, and Abcd2) as well as genes that were expressed comparably in both models (Ly6d, Slpi, Spink3, Scd2, and Cpe).The levels and patterns of mRNA expression of these genes were validated by quantitative RT-PCR analyses.There was a close relationship between the expression levels of Igf2 and H19 mRNA, which were activated in the cirrhotic models.

View Article: PubMed Central - PubMed

Affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.

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Differential gene expression in thioacetamide (TAA)-induced liver tumors and spontaneously developed liver tumors in mice. (a) Histology of liver tissues from TAA-induced and spontaneous tumors. The ages of mice at analyses were 38–40 weeks and 13–15 months in the TAA-induced model and spontaneous model, respectively. HE staining. NT, non-tumor; T, tumor. Scale bar = 50 μm. (b) Quantitative RT-PCR analyses of mRNA expression of 15 tumor-associated genes in TAA-induced and spontaneous (Spont.) tumors. Each value is expressed as the mean ± SEM. The number of samples in each group was 7, 6, 9, 4, and 3 for the TAA control (C), TAA-induced cirrhosis (NT), TAA-induced tumors (T), control C3H mouse liver (NT), and spontaneous tumors (T) in C3H mice, respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control; one-way factorial anova.
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fig05: Differential gene expression in thioacetamide (TAA)-induced liver tumors and spontaneously developed liver tumors in mice. (a) Histology of liver tissues from TAA-induced and spontaneous tumors. The ages of mice at analyses were 38–40 weeks and 13–15 months in the TAA-induced model and spontaneous model, respectively. HE staining. NT, non-tumor; T, tumor. Scale bar = 50 μm. (b) Quantitative RT-PCR analyses of mRNA expression of 15 tumor-associated genes in TAA-induced and spontaneous (Spont.) tumors. Each value is expressed as the mean ± SEM. The number of samples in each group was 7, 6, 9, 4, and 3 for the TAA control (C), TAA-induced cirrhosis (NT), TAA-induced tumors (T), control C3H mouse liver (NT), and spontaneous tumors (T) in C3H mice, respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control; one-way factorial anova.

Mentions: Next, we examined whether similar differential activation could also be observed in other liver tumor models. Thioacetamide-induced selective centrilobular injuries and chronic TAA administration resulted in multiple liver tumors (hepatocellular adenoma or well differentiated HCC), which were associated with marked cirrhosis in the surrounding liver (Fig.5a). In TAA-induced tumors, there were increases in the expression of Igf2 mRNA and Krt20 mRNA, with a tendency for increased mRNA expression of H19 and Igf2bp3 (Fig.5b). In contrast, the mRNA expression of Akr1c18, Gpc3, and Afp, which was highly characteristic of DEN-induced tumors, was not observed in TAA-induced tumors, although there was an increase in Abcd2 mRNA (Fig.5b). In spontaneously formed liver tumors (well to moderately differentiated HCC) in the intact livers of aged C3H mice, there was no increase in the mRNA expression of the genes that were selectively increased in CCl4-induced tumors, but the mRNA expression of Tff3, Akr1c18, Afp, and Abcd2 was significantly increased (Fig.5b). The mRNA expression of all the “common” genes was increased in TAA-induced tumors, whereas that of Spink3, Scd2, and Cpe was lacking in the spontaneously formed tumors (Fig.5b).


Differential reactivation of fetal/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions.

Chen X, Yamamoto M, Fujii K, Nagahama Y, Ooshio T, Xin B, Okada Y, Furukawa H, Nishikawa Y - Cancer Sci. (2015)

Differential gene expression in thioacetamide (TAA)-induced liver tumors and spontaneously developed liver tumors in mice. (a) Histology of liver tissues from TAA-induced and spontaneous tumors. The ages of mice at analyses were 38–40 weeks and 13–15 months in the TAA-induced model and spontaneous model, respectively. HE staining. NT, non-tumor; T, tumor. Scale bar = 50 μm. (b) Quantitative RT-PCR analyses of mRNA expression of 15 tumor-associated genes in TAA-induced and spontaneous (Spont.) tumors. Each value is expressed as the mean ± SEM. The number of samples in each group was 7, 6, 9, 4, and 3 for the TAA control (C), TAA-induced cirrhosis (NT), TAA-induced tumors (T), control C3H mouse liver (NT), and spontaneous tumors (T) in C3H mice, respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control; one-way factorial anova.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig05: Differential gene expression in thioacetamide (TAA)-induced liver tumors and spontaneously developed liver tumors in mice. (a) Histology of liver tissues from TAA-induced and spontaneous tumors. The ages of mice at analyses were 38–40 weeks and 13–15 months in the TAA-induced model and spontaneous model, respectively. HE staining. NT, non-tumor; T, tumor. Scale bar = 50 μm. (b) Quantitative RT-PCR analyses of mRNA expression of 15 tumor-associated genes in TAA-induced and spontaneous (Spont.) tumors. Each value is expressed as the mean ± SEM. The number of samples in each group was 7, 6, 9, 4, and 3 for the TAA control (C), TAA-induced cirrhosis (NT), TAA-induced tumors (T), control C3H mouse liver (NT), and spontaneous tumors (T) in C3H mice, respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control; one-way factorial anova.
Mentions: Next, we examined whether similar differential activation could also be observed in other liver tumor models. Thioacetamide-induced selective centrilobular injuries and chronic TAA administration resulted in multiple liver tumors (hepatocellular adenoma or well differentiated HCC), which were associated with marked cirrhosis in the surrounding liver (Fig.5a). In TAA-induced tumors, there were increases in the expression of Igf2 mRNA and Krt20 mRNA, with a tendency for increased mRNA expression of H19 and Igf2bp3 (Fig.5b). In contrast, the mRNA expression of Akr1c18, Gpc3, and Afp, which was highly characteristic of DEN-induced tumors, was not observed in TAA-induced tumors, although there was an increase in Abcd2 mRNA (Fig.5b). In spontaneously formed liver tumors (well to moderately differentiated HCC) in the intact livers of aged C3H mice, there was no increase in the mRNA expression of the genes that were selectively increased in CCl4-induced tumors, but the mRNA expression of Tff3, Akr1c18, Afp, and Abcd2 was significantly increased (Fig.5b). The mRNA expression of all the “common” genes was increased in TAA-induced tumors, whereas that of Spink3, Scd2, and Cpe was lacking in the spontaneously formed tumors (Fig.5b).

Bottom Line: We identified tumor-associated genes that were expressed differentially in the cirrhotic CCl4 model (H19, Igf2, Cbr3, and Krt20) and the non-cirrhotic DEN model (Tff3, Akr1c18, Gpc3, Afp, and Abcd2) as well as genes that were expressed comparably in both models (Ly6d, Slpi, Spink3, Scd2, and Cpe).The levels and patterns of mRNA expression of these genes were validated by quantitative RT-PCR analyses.There was a close relationship between the expression levels of Igf2 and H19 mRNA, which were activated in the cirrhotic models.

View Article: PubMed Central - PubMed

Affiliation: Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.

Show MeSH
Related in: MedlinePlus