RESUMO
Hypermethylation has been shown in the promoter region of the endothelin receptor B (EDNRB) gene in several human tumors, but its role in lung cancer formation is unclear. In this study, genomic DNA from lung cancer patients was subjected to methylation-specific PCR to determine the methylation status of the EDNRB gene in lung cancer. Aberrant methylation of the EDNRB gene was detected in 32.9% (26 of 79) lung cancer patients. Promoter hypermethylation of EDNRB was found to significantly differ with histological type but was not correlated to other clinicopathological characteristics. Decreased mRNA transcripts were correlated to aberrant methylation. Treatment with 5-aza-deoxycytidine reversed the methylation status and re-expression of the EDNRB gene in the H1355 human lung cancer cell line. Our results suggest that inactivation of the EDNRB gene through epigenetic alteration is highly prevalent in lung cancer in Taiwan.
Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , Receptor de Endotelina B/genética , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Metilação de DNA/efeitos dos fármacos , Decitabina , Regulação para Baixo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Receptor de Endotelina B/metabolismo , Análise de Sequência de DNA , TaiwanRESUMO
Our recent report indicated that HPV infection may be associated with an increased frequency of p16INK4a promoter hypermethylation to cause p16 inactivation. In this study, we further speculated that the HPV infection may be linked with the expression of DNA methyltransferase (DNMT) protein in lung cancer patients and it was observed that an association of p16INK4a promoter hypermethylation with HPV infection existed, but only in female cases (P<0.0001). Interestingly, DNMT3b protein expression was significantly correlated with p16INK4a promoter hypermethylation (P=0.023) and HPV 16/18 infections (P<0.001), respectively. Moreover, the correlation between p16INK4a promoter hypermethylation and DNMT3b protein expression was exclusively seen in female cases (P=0.035). These results strongly suggested that the involvement of HPV infection in nonsmoking female lung tumorigenesis may be mediated, at least to a certain extent, through the increase of DNMT3b protein expression to cause p16INK4a promoter hypermethylation.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA (Citosina-5-)-Metiltransferases/biossíntese , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/virologia , Infecções por Papillomavirus/complicações , Idoso , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fatores Sexuais , DNA Metiltransferase 3BRESUMO
The BRCA1 gene has been shown to be strongly associated with the occurrence of familial breast cancer. The spectrum of BRCA1 gene mutations in breast cancer patients in various populations has been investigated. In this study, patients in Central Taiwan with breast cancer were screened for BRCA1 mutations by sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. Twelve polymorphisms in four exons and three introns were found. One mutation was found in one patient with familial breast cancer. Two patients showed LOH at the locus of BRCA1. Also found in the Taiwanese population were two common haplotypes and one rare haplotype of BRCA1. These results suggest that the mutation of BRCA1 contributes little to the occurrence of breast cancer in the Taiwanese population.
