Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer
Open accessAbstract
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 x wk(-1), 45 min x d(-1), 5% grade at 20 m x min(-1), approximately 0.90 km x d(-1) (TREX1, n = 20) or at 24 m x min(-1), approximately 1.08 km x 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 x d(-1) (mean +/- SD)) or to a nonexercise control (CON-WHL, n = 22). Body composition was measured at approximately 9 wk and serum insulin-like growth factor 1 (IGF-1) at two to three monthly time points beginning at approximately 9 wk on study. Mice were sacrificed when tumors reached 1.5 cm, 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 carcinomas compared with CON-TREX; WHL had a higher tumor 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 on tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer.
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Earlier therapeutic ExTr studies using treadmills failed to show increases in cytotoxic NK or CD8+ T cells.
“Previous therapeutic ExTr interventions (i.e., starting treatment when tumors were established) on running treadmills could not demonstrate enhancement of cytotoxic NK nor CD8+ T cells (7,52,56).”
Exercise dose substantially influences tumor physiology.
“Emerging data suggest that exercise dose plays a significant role in modulating tumor physiology (2,52).”
This strain difference in relative exercise intensity may partly explain why earlier preclinical studies found no antitumor activity with similar ExTr protocols.
“This may explain, at least in part, why previous preclinical studies failed to show antitumor activity under similar ExTr protocols (7,52,56).”
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Koppold, D. A., Kessler, C. S., Steckhan, N., Bähr, V., Kempter, C., Wischnewsky, M., Hübner, M., Kunz, B., Paul, M., Zorn, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13100973
Koppold, D. A., Kessler, C. S., Steckhan, N., Bähr, V., Kempter, C., Wischnewsky, M., Hübner, M., Kunz, B., Paul, M., Zorn, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13100970
Koppold, D. A., Kessler, C. S., Steckhan, N., Bähr, V., Kempter, C., Wischnewsky, M., Hübner, M., Kunz, B., Paul, M., Zorn, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13100976
Tao, Y., Zhou, X., Wang, Q., & Wang, X. (2026) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2026.101128
Exercise against cancer: recent advances and open questions
Plaza‐Florido, A., Rundqvist, H., Galvao, D. A., Pinós, T., Ruiz‐Casado, A., Fiuza‐Luces, C., Schadler, K., Courneya, K. S., & Lucı́a, A. (2026) · Trends in cancer · doi:10.1016/j.trecan.2026.10.003
- Authors
- COLBERT, L. H., WESTERLIND, K. C., PERKINS, S. N., HAINES, D. C., BERRIGAN, D., DONEHOWER, L. A., FUCHS-YOUNG, R., & HURSTING, S. D.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Colorado Denver (US)
- The University of Texas at Austin (US)
- National Cancer Institute (US)
- National Institutes of Health (US)
- Baylor College of Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Medicine & Science in Sports & Exercise
- Published
- 2009-08
- Volume
- 41
- Issue
- 8
- Pages
- 1597-1605
- ISSN
- 0195-9131 (ISSN-L)
- PMC
- PMC3040490
- OpenAlex
- W1989853294
- Cited by
- 60
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 14 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Medicine & Science in Sports & Exercise (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- National Cancer Institute (N01CO12400, N01-CO-012400)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- physical activity, breast cancer, mammary carcinogenesis, p53 deficiency, treadmill running, wheel running, survival, tumor multiplicity, fat mass, insulin-like growth factor I, energy balance, body composition, tumor markers, tumor cell proliferation, cancer cell death
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Animals, Body Composition, Breast Neoplasms, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Female, Insulin-Like Growth Factor I, Mammary Neoplasms, Experimental, Molecular Sequence Data, Physical Conditioning, Animal, Random Allocation, Carcinogenicity Tests, Survival Analysis, Models, Animal, Intracellular Signaling Peptides and Proteins, Mice
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