title: UCP2 knockout suppresses mouse skin carcinogenesis.
abstract: Mitochondrial uncoupling (uncouples electron transport from ATP production) has recently been proposed as a novel survival mechanism for cancer cells, and reduction in free radical generation is the accepted mechanism of action. However, there is no direct evidence supporting that uncoupling proteins promote carcinogenesis. Herein, we examined whether mitochondrial uncoupling affects mouse skin carcinogenesis using uncoupling protein 2 (UCP2) homozygous knockout and wild-type mice. The results indicate that knockout of Ucp2 significantly reduced the formation of both benign (papilloma) and malignant (squamous cell carcinoma) tumors. UCP2 knockout did not cause increases in apoptosis during skin carcinogenesis. The rates of oxygen consumption were decreased only in the carcinogen-treated UCP2 knockout mice, whereas glycolysis was increased only in the carcinogen-treated wild-type mice. Finally, the levels of metabolites pyruvate, malate, and succinate showed different trends after carcinogen treatments between the wild-type and UCP2 knockout mice. Our study is the first to demonstrate that Ucp2 knockout suppresses carcinogenesis in vivo. Together with early studies showing that UCP2 is overexpressed in a number of human cancers, UCP2 could be a potential target for cancer prevention and/or therapy. Cancer Prev Res; 8(6); 487-91. ©2015 AACR.
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana. School of Basic Medicine, Hebei University, Baoding, Hebei, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana. School of Basic Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Kasey
authors.initials: K
authors.lastname: Jackson
authors.affiliation: Department of Pathology, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Xingui
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pathology, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.affiliation: Department of Pathology, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Feist-Weiller Cancer Center, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana.
authors.forename: Runhua
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana. yzhao1@lsuhsc.edu.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D063646:Carcinogenesis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D005260:Female; D016166:Free Radical Scavengers / Q000633:toxicity; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008293:Malates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000502:physiology*; D010101:Oxygen Consumption; D010212:Papilloma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019802:Succinic Acid / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D016166:Free Radical Scavengers; D007473:Ion Channels; D008293:Malates; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D004121:Dimethyl Sulfoxide