Increase in mitochondrial biogenesis, oxidative stress, and glycolysis in murine lymphomas.
Lymphomas adapt to their environment by undergoing a complex series of biochemical changes that are currently not well understood. To better define these changes, we examined the gene expression and gene ontology profiles of thymic lymphomas from a commonly used model of carcinogenesis, the p53(-/-) mouse. These tumors show a highly significant upregulation of mitochondrial biogenesis, mitochondrial protein translation, mtDNA copy number, reactive oxygen species, antioxidant defenses, proton transport, ATP synthesis, hypoxia response, and glycolysis, indicating a fundamental change in the bioenergetic profile of the transformed T cell. Our results suggest that T cell tumorigenesis involves a simultaneous upregulation of mitochondrial biogenesis, mitochondrial respiration, and glycolytic activity. These processes would allow cells to adapt to the stressful tumor environment by facilitating energy production and thereby promote tumor growth. Understanding these adaptations is likely to result in improved therapeutic strategies for this tumor type.
Samper
Enrique
E
The Buck Institute for Age Research, Novato, CA 94945, USA. esamper@cnic.es
Morgado
Lucia
L
Estrada
Juan C
JC
Bernad
Antonio
A
Hubbard
Alan
A
Cadenas
Susana
S
Melov
Simon
S
D000818:Animals; D004272:DNA, Mitochondrial / Q000032:analysis*; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010101:Oxygen Consumption; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53