Exercise Effects on Tumorigenesis in a p53-Deficient Mouse Model of Breast Cancer

COLBERT, L. H., K. C. WESTERLIND, S. N. PERKINS, D. C. HAINES, D. BERRIGAN, L. A. DONEHOWER, R. FUCHS-YOUNG, and S. D. HURSTING. Exercise Effects on Tumorigenesis in a p53-Deficient Mouse Model of Breast Cancer. Med. Sci. Sports Exerc., Vol. 41, No. 8, pp 1597-1605, 2009. Purpose: Physically active women have a reduced risk of breast cancer, but the dose of activity necessary and the role of energy balance and other potential mechanisms have not been fully explored in animal models. We examined treadmill and wheel running effects on mammary tumorigenesis and biomarkers in p53-deficient (p53(+/-)):MMTV-Wnt-1 transgenic mice. Methods: Female mice (9 wk old) were randomly assigned to the following groups in experiment 1: treadmill exercise 5 d.wk(-1), 45 min.d(-1), 5% grade at 20 m.min(-1), similar to 0.90 km.d(-1) (TREX1, n = 20) or at 24 m.min(-1), similar to 1.08 km.d(-1) (TREX2, n = 21) or a nonexercise control (CON-TREX, n = 22). In experiment 2, mice were randomly assigned to voluntary wheel running (WHL, n = 21, 2.46 +/- 1.11 km.d(-1) (mean +/- SD)) or to a nonexercise control (CON-WHL, n = 22). Bodycomposition was measured at similar to 9 wk and serum insulin-like growth factor 1 (IGF-1) at two to three monthly time points beginning at similar to 9 wk on study. Mice were sacrificed when tumors reached 1.5 cut, mice became moribund, or there was only one mouse per treatment group remaining. Results: TREX1 (24 wk) and TREX2 (21 wk) had shorter median survival times than CON-TREX (34 wk, P < 0.01), whereas those of WHL and CON-WHL were similar (23 vs 24 wk: P = 0.32). TREX2 had increased multiplicity of mammary gland carcinoma compared with CON-TREX, WHL had a higher turner incidence than CON-WHL. All exercising animals were lighter than their respective controls. and WHL had lower body fat than CON-WHL (P < 0.01). There was no difference in IGF-1 between groups (P > 0.05). Conclusions: Despite beneficial or no effects on body weight, body fat, or IGF-1, exercise had detrimental effects Oil tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer.

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