کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1905032 | 1534687 | 2012 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype](/preview/png/1905032.png)
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 ρ0 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.
► Cybrids are useful models to study the role of mtDNA changes in cancer development.
► Somatic mutations in mtDNA produce changes in cellular growth and motility.
► There are mtDNA-driven differences in production of intracellular ROS.
► Antioxidants were able to diminish the tumorigenic phenotypes of mutant cybrids.
► Mutations in mtDNA play important roles in the development of neoplasia.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1822, Issue 2, February 2012, Pages 293–300