Mitochondria and tumors: A new perspective.
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Date
2013-07
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Abstract
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. MATERIALS AND 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. CONCLUSION: 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.
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Keywords
Breast Tumor, hemangioma, mitochondria, OXPHOS gene defects, tumors
Citation
Chintha R, Kaipa P R, Sekhar N, Hasan Q. Mitochondria and tumors: A new perspective. Indian Journal of Cancer. 2013 July-Sept; 50(3): 206-213.