Document Detail

Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis.
MedLine Citation:
PMID:  15979824     Owner:  NLM     Status:  MEDLINE    
Mitochondrial dysfunction is a hallmark of cancer cells. Consistent with this phenotype mutations in mitochondrial genome have been reported in all cancers examined to date. However, it is not clear whether mitochondrial genomic status in human cells affects nuclear genome stability and whether proteins involved in inter-genomic cross talk are involved in tumorigenesis. Using cell culture model and cybrid cell technology, we provide evidence that mitochondrial genetic status impacts nuclear genome stability in human cells. In particular our studies demonstrate 1) that depletion of mitochondrial genome (rho0) leads to chromosomal instability (CIN) reported to be present in variety of human tumors and 2) rho0 cells show transformed phenotype. Our study also demonstrates that mitochondrial genetic status plays a key role in regulation of a multifunctional protein APE1 (also known as Ref1 or HAP1) involved in transcription and DNA repair in the nucleus and the mitochondria. Interestingly we found that altered expression of APE1 in rho0 cells and tumorigenic phenotype can be reversed by exogenous transfer of wild type mitochondria in rho0 cells. Furthermore, we demonstrate that APE1 expression is altered in variety of primary tumors. Taken together, these studies suggest that inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis and that APE1 mediates this process.
Keshav K Singh; Mariola Kulawiec; Ivan Still; Mohamed M Desouki; Joseph Geradts; Sei-Ichi Matsui
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gene     Volume:  354     ISSN:  0378-1119     ISO Abbreviation:  Gene     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-08-16     Completed Date:  2005-12-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  140-6     Citation Subset:  IM    
Department of Cancer Genetics, Cell and Virus Building, Room 247, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
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MeSH Terms
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Nucleus / genetics*
Chromosome Aberrations
DNA, Mitochondrial / genetics*
DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
Hybrid Cells
Neoplasms / genetics,  metabolism,  pathology
Signal Transduction / genetics*
Spectral Karyotyping
Tissue Array Analysis
Translocation, Genetic
Grant Support
R01-097714//PHS HHS
Reg. No./Substance:
0/DNA, Mitochondrial; EC or Apyrimidinic Site) Lyase

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