title: Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype.
abstract: 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.
authors: Southern Arizona VA Healthcare System and Department of Medicine, Dermatology Division, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors: Jana
authors: J
authors: Jandova
authors: Mingjian
authors: M
authors: Shi
authors: Kimberly G
authors: KG
authors: Norman
authors: George P
authors: GP
authors: Stricklin
authors: James E
authors: JE
authors: Sligh
mesh_terms: D000483:Alleles; D022981:Allelic Imbalance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D019069:Cell Respiration / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D056426:Genetic Loci; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006822:Hybrid Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D012343:RNA, Transfer / Q000235:genetics
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D012343:RNA, Transfer; D001120:Arginine