title: Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells.
abstract: Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (rho(0)) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties.
authors.affiliation: Institute of Biological Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Akimoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Niikura
authors.forename: Masami
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Honma
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology; D019069:Cell Respiration; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D046528:Chimerism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts; D016678:Genome; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype
chemical_list: D002273:Carcinogens; D004272:DNA, Mitochondrial; D008748:Methylcholanthrene; D004247:DNA