Work

Cancer Preventive Mechanisms by Exercise: Activation of p53 and p53‐related IGF‐1 Pathway Regulators

Year: 2015

Type: article

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 is to investigate the effects of exercise on p53 and p53-related proteins engaged in IGF-1 pathway regulation in skin epidermis. Female SENCAR mice were fed an iso-caloric diet with or without 10-week treadmill exercise at 20 m/min for 60 min daily. Animals were treated with TPA topically 2 hours before sacrifice and the target proteins in the epidermis were assessed. All the target proteins except for MDM2 decreased under TPA treatment versus vehicle acetone as measured by immunohistochemistry and/or Western blot. A significant increase of p53 but decrease of MDM2 was observed in exercised group when compared with sedentary control. Additionally, p53-related downstream proteins such as p21, IGF-BP3, and PTEN increased significantly in response to exercise. Taken together, exercise appears to activate p53 by reducing MDM2 suppression, resulting in enhanced expression of IGF-BP3, p21, and PTEN. Both IGF-BP3 and PTEN may further reduce bioavailable IGF-1 and IGF-1-dependent signaling. A negative regulation of IGF-1 pathway through p53 activation and p53-related regulators may thus contribute to the observed cancer prevention by exercise in this mouse skin cancer model (supported by NIH CA167678).

Source: The FASEB Journal

DOI: 10.1096/fasebj.29.1_supplement.752.13