title: Lower expression of p14ARF and p16INK4a correlates with higher DNMT3B expression in human oesophageal squamous cell carcinomas.
abstract: Oesophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and is the sixth cause of cancer-related death in the world. Inactivation of cell-cycle regulating genes, such as p14ARF and p16INK4a, and cell adhesion genes, such as E-cadherin, is common in cancer, and results from genetic and/or epigenetic alterations. Therefore, we have analysed the mRNA expression of p14ARF, p16INK4a and E-cadherin in 17 matched ESCC and normal mucosal samples obtained from Brazilian patients by semi-quantitative RT-PCR. The expression of p14ARF and p16INK4a was absent or reduced in several ESCC samples. Hypermethylation of CpG islands, caused by the action of DNA methyltransferases (DNMTs), is a major form of epigenetic inactivation of the p14ARF and p16INK4a genes in tumours. Hence, we also investigated the mRNA expression of the human DNA methyltransferases in normal oesophageal mucosa and in the tumour matched samples. All DNMTs were constitutively expressed in the normal oesophageal mucosa but a significantly higher expression of DNMT3B was observed in the tumours. Data analysis by the Spearman rank test showed that the expression of DNMT3B was inversely correlated with that of p14ARF and p16INK4a. Our results suggest that DNMT3B over-expression may be involved in the suppression or lower expression of p14ARF and p16INK4a observed in ESCC.
authors.affiliation: Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana de Almeida
authors.initials: Tde A
authors.lastname: Simão
authors.forename: Gabriela Loureiro De Bonis Almeida
authors.initials: GL
authors.lastname: Simões
authors.forename: Fabiana Siqueira
authors.initials: FS
authors.lastname: Ribeiro
authors.forename: Daniela Anhel de Paula
authors.initials: DA
authors.lastname: Cidade
authors.forename: Nelson Adami
authors.initials: NA
authors.lastname: Andreollo
authors.forename: Luiz Roberto
authors.initials: LR
authors.lastname: Lopes
authors.forename: Jacyara Maria Brito
authors.initials: JM
authors.lastname: Macedo
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Acatauassu
authors.forename: Ana Maria Rossini
authors.initials: AM
authors.lastname: Teixeira
authors.forename: Israel
authors.initials: I
authors.lastname: Felzenszwalb
authors.forename: Luis Felipe Ribeiro
authors.initials: LF
authors.lastname: Pinto
authors.forename: Rodolpho Mattos
authors.initials: RM
authors.lastname: Albano
mesh_terms: D000368:Aged; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008745:Methylation; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*; D000097584:DNA Methyltransferase 3B
chemical_list: D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D000097584:DNA Methyltransferase 3B