title: Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within a Skin Cancer Model.
abstract: Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Miao
authors: M
authors: Yu
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Brenee
authors: B
authors: King
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Emily
authors: E
authors: Ewert
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Xiaoyu
authors: X
authors: Su
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Nur
authors: N
authors: Mardiyati
authors: Institute for Agri-food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai, China.
authors: Zhihui
authors: Z
authors: Zhao
authors: Department of Food Nutrition Dietetics & Health, Kansas State University, Manhattan, Kansas, United States of America.
authors: Weiqun
authors: W
authors: Wang
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D018632:Mice, Inbred SENCAR; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010703:Phorbol Esters / Q000633:toxicity; D010805:Physical Conditioning, Animal; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D018972:Insulin-Like Growth Factor Binding Protein 3; D010703:Phorbol Esters; D016159:Tumor Suppressor Protein p53; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; C000600213:12-O-undecadienoylphorbol-13-acetate; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse