title: DNA methyltransferases 3a and 3b are differentially expressed in the early stages of a rat liver carcinogenesis model.
abstract: Carcinogenesis is driven by the accumulation of mutations and abnormal DNA methylation patterns, particularly the hypermethylation of tumor‑suppressor genes. Changes in genomic DNA methylation patterns are established by the DNA methyltransferases (DNMTs) family: DNMT1, DNMT3a and DNMT3b. The DNMTs are known to be overexpressed in tumors. However, when the DNMTs expression profile is altered in earlier stages of carcinogenesis remains to be elucidated. The resistant hepatocyte model (RHM) allows the analysis of the hepatocellular carcinoma (HCC) from the formation of altered cell foci to the appearance of tumors in rats. To investigate the DNMTs expression in this model, we first observed that timp3, rassf1a and p16 genes became methylated during cancer development by methylation‑specific PCR (MSP) and the bisulphate sequencing PCR (BSP) of timp3. The differential expression at the RNA and protein level of the three DNMTs was also assessed. dnmt1 expression was higher in tumors than in normal and early cancer stages. However, no evident overexpression of the enzyme was identified by immunohistochemistry. By contrast, DNMT3a and DNMT3b were consistently subexpressed in tumors. In the present study, we report a carcinogenesis model that does not feature the overexpression of DNMT1 but exhibits a transient expression of DNMT3a and DNMT3b.
authors.affiliation: Department of Cell Biology Center for Research and Advanced Studies (CINVESTAV) IPN, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Valencia Antúnez
authors.affiliation: National Cancer Institute, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Lucía
authors.initials: L
authors.lastname: Taja Chayeb
authors.affiliation: Department of Physics, Center for Research and Advanced Studies (CINVESTAV) IPN, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Rodríguez-Segura
authors.affiliation: Department of Cell Biology Center for Research and Advanced Studies (CINVESTAV) IPN, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Guadalupe Soledad
authors.initials: GS
authors.lastname: López Álvarez
authors.affiliation: National Cancer Institute, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: García-Cuéllar
authors.affiliation: Department of Cell Biology Center for Research and Advanced Studies (CINVESTAV) IPN, Basic Research Branch, Mexico, D.F., Mexico.
authors.forename: Saúl
authors.initials: S
authors.lastname: Villa Treviño
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004052:Diethylnitrosamine; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051381:Rats; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D015073:2-Acetylaminofluorene; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004052:Diethylnitrosamine; D019717:Tissue Inhibitor of Metalloproteinase-3; D025521:Tumor Suppressor Proteins; D000097584:DNA Methyltransferase 3B; C560857:RASSF1 protein, rat