Mitochondrial regulation of cancer associated nuclear DNA methylation.
Biochem Biophys Res Commun
; 364(3): 656-61, 2007 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-17964537
ABSTRACT
The onset and progression of cancer is associated with the methylation-dependent silencing of specific genes, however, the mechanism and its regulation have not been established. We previously demonstrated that reduction of mitochondrial DNA content induces cancer progression. Here we found that mitochondrial DNA-deficient LNrho0-8 activates the hypermethylation of the nuclear DNA promoters including the promoter CpG islands of the endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin. These are unmethylated and the corresponding gene products are expressed in the parental LNCaP containing mitochondrial DNA. The absence of mitochondrial DNA induced DNA methyltransferase 1 expression which was responsible for the methylation patterns observed. Inhibition of DNA methyltransferase eliminated hypermethylation and expressed gene products in LNrho0-8. These studies demonstrate loss or reduction of mitochondrial DNA resulted in the induction of DNA methyltransferase 1, hypermethylation of the promoters of endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin, and reduction of the corresponding gene products.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
DNA Mitocondrial
/
DNA de Neoplasias
/
Núcleo Celular
/
Ilhas de CpG
/
Metilação de DNA
/
Mitocôndrias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos