Document Detail

Mitochondrial regulation of cancer associated nuclear DNA methylation.
MedLine Citation:
PMID:  17964537     Owner:  NLM     Status:  MEDLINE    
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.
Cheng-hui Xie; Akihiro Naito; Takatsugu Mizumachi; Teresa T Evans; Michael G Douglas; Craig A Cooney; Chun-Yang Fan; Masahiro Higuchi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-10-16
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  364     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-07     Completed Date:  2007-12-18     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  656-61     Citation Subset:  IM    
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MeSH Terms
Cell Line, Tumor
Cell Nucleus / genetics*
CpG Islands / genetics*
DNA Methylation*
DNA, Mitochondrial / genetics*
DNA, Neoplasm / genetics*
Mitochondria / genetics*
Prostatic Neoplasms / genetics*
Grant Support
CA100846/CA/NCI NIH HHS; R01 CA100846/CA/NCI NIH HHS; R01 CA100846-01A1/CA/NCI NIH HHS; R01 CA100846-02/CA/NCI NIH HHS; R01 CA100846-03/CA/NCI NIH HHS; R01 CA100846-04/CA/NCI NIH HHS; R01 CA100846-05/CA/NCI NIH HHS; R01 CA100846-06/CA/NCI NIH HHS
Reg. No./Substance:
0/DNA, Mitochondrial; 0/DNA, Neoplasm

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