RESUMO
Although leukoplakia is the most common precancerous lesion of the oral cavity, its molecular biological properties are largely unknown. The aim of this study was to identify the genes responsible for its pathogenesis and malignant transformation using oligonucleotide microarray technology. The expression profiles of 8,800 genes in human oral leukoplakia (n=4) and oral squamous cell carcinoma (OSCC) (n=2) were analyzed using the Affymetrix GeneChip system and the results were confirmed with RT-PCR. Eight genes were up-regulated (>2.0-fold) and ten were down-regulated (<0.5-fold) in all leukoplakias analyzed with the GeneChip. In particular, loricrin and keratins displayed greater differences between normal tissue and leukoplakia. Some of the 18 alternatively expressed genes were markedly down-regulated in squamous cell carcinoma compared with leukoplakia. Our data suggested that gene abnormalities in cytoskeleton network components might be responsible for the development and progression of oral leukoplakia.
Assuntos
Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Leucoplasia Oral/genética , Neoplasias Bucais/genética , Idoso , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genoma Humano , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genéticaRESUMO
5-fluorouracil (5-FU) has been widely used for chemotherapy of head and neck cancer, and is known to affect the cell cycle and induce apoptotic death of cancer cells. However, the molecular actions of 5-FU on the cell cycle regulatory mechanism have not been fully explained. Herein we analyzed the effects of 5-FU on the expression of G1/S-related cell cycle regulators in oral cancer cell lines. In vitro 5-FU treatment of oral cancer cells resulted in an increase in G1/S phase cells. p21 expression was augmented by 5-FU without any notable changes in p53 expression. A remarkable up-regulation of cyclin E and a concomitant down-regulation of cyclin D were observed after 24 h 5-FU treatment. Our results suggest that 5-FU-induced changes in cell cycle regulation of oral cancer cells might associate with an alteration of G1 cyclins expression. p21 was remarkably up-regulated, but it was speculated that its activity might be cancelled by an increased binding to CDK4.