Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype.
| Autor: | Jandova J; Southern Arizona VA Healthcare System and Department of Medicine, Dermatology Division, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA., Shi M, Norman KG, Stricklin GP, Sligh JE |
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| Jazyk: | angličtina |
| Zdroj: | Biochimica et biophysica acta [Biochim Biophys Acta] 2012 Feb; Vol. 1822 (2), pp. 293-300. Date of Electronic Publication: 2011 Nov 15. |
| DOI: | 10.1016/j.bbadis.2011.11.010 |
| Abstrakt: | There have been many reports of mitochondrial DNA (mtDNA) mutations associated with human malignancies. We have observed allelic instability in UV-induced cutaneous tumors at the mt-Tr locus encoding the mitochondrial tRNA for arginine. We examined the effects of somatic alterations at this locus by modeling the change in a uniform nuclear background by generating cybrids harboring allelic variation at mt-Tr. We utilized the naturally occurring mtDNA variation at mt-Tr within the BALB/cJ (BALB) and C57BL/6J (B6) strains of Mus musculus to transfer their mitochondria into a mouse ρ(0) cell line that lacked its own mtDNA. The BALB haplotype containing the mt-Tr 9821insA allele produced significant changes in cellular respiration (resulting in lowered ATP production), but increased rates of cellular proliferation in cybrid cells. Furthermore, the mtDNA genotype associated with UV-induced tumors endowed the cybrid cells with a phenotype of resistance to UV-induced apoptosis and enhanced migration and invasion capabilities. These studies support a role for mtDNA changes in cancer. (Copyright © 2011 Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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