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Human & Experimental Toxicology, Vol. 25, No. 9, 515-522 (2006)
DOI: 10.1191/0960327106het649oa

Lower expression of p14ARF and p16INK4a correlates with higher DNMT3B expression in human oesophageal squamous cell carcinomas

Tatiana de Almeida Simão

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Gabriela Loureiro De Bonis Almeida Simões

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Fabiana Siqueira Ribeiro

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Daniela Anhel de Paula Cidade

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Nelson Adami Andreollo

Departamento de Cirurgia e Gastrocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil

Luiz Roberto Lopes

Departamento de Cirurgia e Gastrocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil

Jacyara Maria Brito Macedo

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Rodolfo Acatauassu

Serviço de Cirurgia Torácica, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, RJ, Brazil

Ana Maria Rossini Teixeira

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Israel Felzenszwalb

Departamento de Biofísica e Biometria, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Luis Felipe Ribeiro Pinto

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Rodolpho Mattos Albano

Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil, albano{at}uerj.br

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.

Key Words: cancer • DNMT • oesophagus • p14ARF • p16INK4a


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