Effect of Nonmotorized Wheel Running on Mammary Carcinogenesis: Circulating Biomarkers, Cellular Processes, and Molecular Mechanisms in Rats
The objective of this experiment was to identify circulating growth factors, hormones, and cellular and molecular mechanisms that account for the effects of physical activity on mammary carcinogenesis. A total of 120 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and...
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| Published in: | Cancer epidemiology, biomarkers & prevention Vol. 17; no. 8; pp. 1920 - 1929 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Philadelphia, PA
American Association for Cancer Research
01-08-2008
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | The objective of this experiment was to identify circulating growth factors, hormones, and cellular and molecular mechanisms
that account for the effects of physical activity on mammary carcinogenesis. A total of 120 female Sprague-Dawley rats were
injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either a physically active or a sedentary
control group. Individually housed rats were given free access to a nonmotorized, computer-controlled activity wheel and running
behavior was reinforced by food reward. Rats self-determined their daily intensity and duration of running. Sedentary control
rats received the same amount of food as the physically active rats to which they were paired. Physical activity reduced mammary
cancer incidence ( P = 0.015) and cancer multiplicity ( P = 0.01). Physical activity induced changes in plasma insulin, insulin-like growth factor-I, and corticosterone, suggesting
that mechanisms regulating glucose homeostasis were affected. Western blot analyses of mammary carcinomas revealed that proteins
involved in cell proliferation were reduced ( P < 0.001) and those involved in apoptosis via the mitochondrial pathway were elevated ( P < 0.001) by physical activity. The hypothesis that these effects were mediated by activation of AMP-activated protein kinase,
and down-regulation of protein kinase B, which collectively down-regulate the activity of the mammalian target of rapamycin,
was evaluated. Evidence in support of this hypothesis was found in the Western blot analyses of mammary carcinomas, mammary
gland, liver, and skeletal muscle. Collectively, these findings provide a rationale for additional studies of energy-sensing
pathways in the elucidation of mechanisms that account for the inhibition of carcinogenesis by physical activity. (Cancer
Epidemiol Biomarkers Prev 2008;17(8):1920–9) |
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| ISSN: | 1055-9965 1538-7755 |
| DOI: | 10.1158/1055-9965.EPI-08-0175 |