Mitochondria and tumors: a new perspective.
BACKGROUND
Mitochondrial DNA (Mt DNA) defects have been identified in a variety of Tumors, but the exact role of these defects in the pathogenicity and tumor progression is poorly understood. This study aims at identifying the status of mitochondrial OXPHOS genes in neoplastic transformation and attempts to establish a cause and effect relationship between mitochondrial OXPHOS defects and tumor progression.


METHODS
Mutational, expression and functional analysis of l2 of the 13 mitochondrial OXPHOS genes has been carried out using PCR, Real-Time PCR and protein modeling in 180 sporadic samples of a heterogeneous group of benign and malignant tumors like that of benign, malignant, matched blood and adjacent normal tissue of breast and benign hemangioma.


RESULTS
Mutations were identified in the ND4L, ND6 and COX-II regions of the mitochondrial OXPHOS genes. All the mutations were limited only to the malignant breast tissues. On relative quantification, a compromised expression of OXPHOS genes was identified in all the malignant tissues irrespective of their mutational states. Protein modeling revealed loss of function mutations of ND6 and COX-II proteins.


CONCLUSIONS
This is the first study worldwide wherein a comparative study using different benign and malignant tumors has been carried out to assess the role of Mt DNA defects. Our data reveals mitochondrial dysfunction only in malignant cells and not in their benign counterparts, indicating that the dysfunction may arise after the pro-proliferative pathway has set in. We hypothesize that compromised OXPHOS may be a responsive mechanism of the cell to counter cancers, rather than a mechanism of initiating tumorigenesis.
Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India.
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Chintha
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Kaipa
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Sekhar
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Hasan
D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D050259:Genes, Mitochondrial / Q000235:genetics*; D006801:Humans; D009245:NADH Dehydrogenase / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D010085:Oxidative Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004272:DNA, Mitochondrial; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV