Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Adicionar filtros








Intervalo de ano
1.
Chinese Journal of Pathology ; (12): 433-436, 2004.
Artigo em Chinês | WPRIM | ID: wpr-283496

RESUMO

<p><b>OBJECTIVE</b>To assess the role of methylated mismatch repair (MMR) genes (hMLH1, hMSH2 and hMSH3) in the carcinogenesis and progression of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Samples of 38 cases of HCC along with their corresponding noncancerous tissues, 2 samples of donated normal tissue and 6 cell lines were collected and subject to the methylation-specific PCR (MSP) to examine promoter methylation status of MLH1, MSH2 and MSH3. Six tumor cell lines were analyzed before and after 5-aza-2'-deoxycytidine treatment. In addition, alterations of mRNA expression of MMRs were investigated by quantitative reverse transcription-PCR.</p><p><b>RESULTS</b>CpG island methylation of hMLH1 and hMSH2 was observed in 13.2% (5 of 38 samples) and 68.4% (26 of 38 samples) respectively in HCC, 2.6% (1 of 38 samples) and 55.3% (21 of 38) respectively in corresponding noncancerous tissues, but not in normal control tissues. Promoter methylation of the hMSH2 gene was present in 83.3% of cell lines tested (5/6), but none were observed for the hMLH1 gene. Promoter methylation of the hMSH3 gene was not identified in any tissue samples or cell lines. After 5-aza-2'-deoxycytidine treatment, hMSH2 methylation was induced or completely reversed, and its mRNA expression was increased in most cell lines.</p><p><b>CONCLUSIONS</b>Our results suggest that promoter hypermethylation of hMLH1 and hMSH2 genes is common in HCC. Particularly, there is a high frequency of methylation of hMSH2 in both cancer and noncancerous tissues, but not in normal control tissue. Therefore, hypermethylation of MMR genes, especially hMSH2, may be involved in the carcinogenesis of HCC and may serve as an early diagnostic marker for HCC. The close correlation between hMSH2 methylation and low expression of its mRNA suggests that hMSH2 methylation is an important pathway in the regulation of gene expression.</p>


Assuntos
Humanos , Proteínas Adaptadoras de Transdução de Sinal , Azacitidina , Farmacologia , Pareamento Incorreto de Bases , Genética , Carcinoma Hepatocelular , Genética , Proteínas de Transporte , Genética , Linhagem Celular Tumoral , Metilação de DNA , Metilases de Modificação do DNA , Reparo do DNA , Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Genética , Proteína 1 Homóloga a MutL , Proteínas MutL , Proteínas de Neoplasias , Genética , Proteínas Nucleares , Genética , RNA Mensageiro , Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA