Inactivation of TPEF Gene by Aberrant Methylation in Hepatocellular Carcinoma
Korean Journal of Pathology
; : 9-15, 2008.
Article
em Ko
| WPRIM
| ID: wpr-94449
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND: Abnormalities of genomic methylation patterns have been shown to play a role in the development of carcinoma, and the silencing of tumor suppressor genes is related to local de novo methylation. METHODS: Using methylation specific arbitrarily primed-Polymerase Chain Reaction (Ms AP-PCR), we identified a 322 bp sequence that contained a 5' un-translated and exon1 regions of the TPEF gene. To evaluate the inactivation of the TPEF gene through hypermethylation in hepatocellular carcinoma (HCC), we investigated the correlation between methylation patterns and TPEF expression in tumor tissues of human HCC and cell lines via a Combined Bisulfite Restriction Assay (CoBRA) and RT-PCR. RESULTS: A dense methylation pattern of the TPEF was detected in most cell lines, as well as in 10 of the 14 (71.4%) HCC tissues. In addition, loss of heterozygosity (LOH) from the TPEF gene was observed in 5 of the 14 (36%) HCC tissues. Furthermore, RT-PCR analysis revealed TPEF expression in 5 of 8 (62.5%) cell lines. Finally, treatment with a demethylating agent, 5-Aza- 2'-deoxycitidine (5-AzaC), increased the expression of TPEF mRNA. CONCLUSION: These results indicate that inactivation of the TPEF gene through hypermethylation may be a mechanism by which tumorigenesis occurs in HCC.
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Base de dados:
WPRIM
Assunto principal:
Transformação Celular Neoplásica
/
Genes Supressores de Tumor
/
Carcinoma Hepatocelular
Limite:
Humans
Idioma:
Ko
Revista:
Korean Journal of Pathology
Ano de publicação:
2008
Tipo de documento:
Article