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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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Fetal/neonatal activation of tumor-associated genes and their products. (a) Quantitative RT-PCR analyses of mRNA expression of tumor-associated genes during fetal/neonatal periods. Each value is expressed as the mean ± SEM. The number of samples in each group was 3, 5, 7, 10, 4, 4, 4, and 7 for E13.5, E16.5, P0 (immediately after birth), P1 (1 day after birth), P3 (3 days after birth), P6 (6 days after birth), 1 m (1 month old), and 5 m (5 months old), respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control (5 m); one-way factorial anova. (b) In situ detection of insulin-like growth factor 2 (IGF2), H19 mRNA, trefoil factor 3 (TFF3), and α-fetoprotein (AFP) in developing livers. Immunohistochemistry for IGF2, TFF3, and AFP and in situ hybridization for H19 mRNA in fetal (E16.5) and neonatal (P0) livers. Scale bar = 20 μm.
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fig04: Fetal/neonatal activation of tumor-associated genes and their products. (a) Quantitative RT-PCR analyses of mRNA expression of tumor-associated genes during fetal/neonatal periods. Each value is expressed as the mean ± SEM. The number of samples in each group was 3, 5, 7, 10, 4, 4, 4, and 7 for E13.5, E16.5, P0 (immediately after birth), P1 (1 day after birth), P3 (3 days after birth), P6 (6 days after birth), 1 m (1 month old), and 5 m (5 months old), respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control (5 m); one-way factorial anova. (b) In situ detection of insulin-like growth factor 2 (IGF2), H19 mRNA, trefoil factor 3 (TFF3), and α-fetoprotein (AFP) in developing livers. Immunohistochemistry for IGF2, TFF3, and AFP and in situ hybridization for H19 mRNA in fetal (E16.5) and neonatal (P0) livers. Scale bar = 20 μm.

Mentions: Because the identified tumor-associated genes included well-known oncofetal genes, such as Igf2, H19, Gpc3, and Afp, we examined their mRNA expression during fetal and neonatal periods. Our results clearly showed that all of these genes, with the exceptions of Cbr3 and Cpe, were highly expressed in either the fetal or neonatal periods (Fig.4a), indicating that the differential activation of fetal/neonatal gene expression occurs in CCl4- and DEN-induced liver tumors. As expected, the protein expression of IGF2 and TFF3 and the mRNA expression of H19 were detected in hepatoblasts/hepatocytes during the fetal or neonatal period (Fig.4b).


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)

Fetal/neonatal activation of tumor-associated genes and their products. (a) Quantitative RT-PCR analyses of mRNA expression of tumor-associated genes during fetal/neonatal periods. Each value is expressed as the mean ± SEM. The number of samples in each group was 3, 5, 7, 10, 4, 4, 4, and 7 for E13.5, E16.5, P0 (immediately after birth), P1 (1 day after birth), P3 (3 days after birth), P6 (6 days after birth), 1 m (1 month old), and 5 m (5 months old), respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control (5 m); one-way factorial anova. (b) In situ detection of insulin-like growth factor 2 (IGF2), H19 mRNA, trefoil factor 3 (TFF3), and α-fetoprotein (AFP) in developing livers. Immunohistochemistry for IGF2, TFF3, and AFP and in situ hybridization for H19 mRNA in fetal (E16.5) and neonatal (P0) livers. Scale bar = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556385&req=5

fig04: Fetal/neonatal activation of tumor-associated genes and their products. (a) Quantitative RT-PCR analyses of mRNA expression of tumor-associated genes during fetal/neonatal periods. Each value is expressed as the mean ± SEM. The number of samples in each group was 3, 5, 7, 10, 4, 4, 4, and 7 for E13.5, E16.5, P0 (immediately after birth), P1 (1 day after birth), P3 (3 days after birth), P6 (6 days after birth), 1 m (1 month old), and 5 m (5 months old), respectively. *P < 0.05, **P < 0.01, ***P < 0.001 versus control (5 m); one-way factorial anova. (b) In situ detection of insulin-like growth factor 2 (IGF2), H19 mRNA, trefoil factor 3 (TFF3), and α-fetoprotein (AFP) in developing livers. Immunohistochemistry for IGF2, TFF3, and AFP and in situ hybridization for H19 mRNA in fetal (E16.5) and neonatal (P0) livers. Scale bar = 20 μm.
Mentions: Because the identified tumor-associated genes included well-known oncofetal genes, such as Igf2, H19, Gpc3, and Afp, we examined their mRNA expression during fetal and neonatal periods. Our results clearly showed that all of these genes, with the exceptions of Cbr3 and Cpe, were highly expressed in either the fetal or neonatal periods (Fig.4a), indicating that the differential activation of fetal/neonatal gene expression occurs in CCl4- and DEN-induced liver tumors. As expected, the protein expression of IGF2 and TFF3 and the mRNA expression of H19 were detected in hepatoblasts/hepatocytes during the fetal or neonatal period (Fig.4b).

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