A specific nuclear DNA background is required for high frequency lymphoma development in transmitochondrial mice with G13997A mtDNA.
We previously found that mouse mitochondrial DNA (mtDNA) with a G13997A mutation (G13997A mtDNA) controls not only the transformation of cultured lung carcinoma cells from poorly metastatic into highly metastatic cells, but also the transformation of lymphocytes into lymphomas in living C57BL/6 (B6) mice. Because the nuclear genetic background of the B6 strain makes the strain prone to develop lymphomas, here we examined whether G13997A mtDNA independently induces lymphoma development even in mice with the nuclear genetic background of the A/J strain, which is not prone to develop lymphomas. Our results showed that the B6 nuclear genetic background is required for frequent lymphoma development in mice with G13997A mtDNA. Moreover, G13997A mtDNA in mice did not enhance the malignant transformation of lung adenomas into adenocarcinomas or that of hepatocellular carcinomas from poorly metastatic into highly metastatic carcinomas. Therefore, G13997A mtDNA enhances the frequency of lymphoma development under the abnormalities in the B6 nuclear genome, and does not independently control tumor development and tumor progression.
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Osamu
O
Hashizume
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Haruka
H
Yamanashi
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyou-ku, Kyoto, Japan.
Makoto M
MM
Taketo
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Kazuto
K
Nakada
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan; TARA center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Jun-Ichi
J
Hayashi
D055372:AMP-Activated Protein Kinases; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D000068617:Genetic Background; D023281:Genomics; D007178:Inbreeding; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000235:genetics*; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D014520:Urethane / Q000009:adverse effects
D004272:DNA, Mitochondrial; D014520:Urethane; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases