Inherent aerobic capacity-dependent differences in breast carcinogenesis

Although regular physical activity is associated with improvement in aerobic capacity and lower breast cancer risk, there are heritable sets of traits that affect improvement in aerobic capacity in response to physical activity. Although aerobic capacity segregates risk for a number of chronic disea...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2017-09, Vol.38 (9), p.920-928
Main Authors: Thompson, Henry J, Jones, Lee W, Koch, Lauren G, Britton, Steven L, Neil, Elizabeth S, McGinley, John N
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - metabolism
Animals
Biomarkers, Tumor - blood
Carcinogenesis - chemically induced
Carcinogenesis - genetics
Female
Inflammation, Microenvironment and Prevention
Mammary Neoplasms, Experimental - chemically induced
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - metabolism
Methylnitrosourea - pharmacology
Physical Conditioning, Animal
Proto-Oncogene Proteins c-akt - metabolism
Rats
Risk Factors
TOR Serine-Threonine Kinases - metabolism
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Summary:Although regular physical activity is associated with improvement in aerobic capacity and lower breast cancer risk, there are heritable sets of traits that affect improvement in aerobic capacity in response to physical activity. Although aerobic capacity segregates risk for a number of chronic diseases, the effect of the heritable component on cancer risk has not been evaluated. Therefore, we investigated breast carcinogenesis in rodent models of heritable fitness in the absence of induced physical activity. Female offspring of N:NIH rats selectively bred for low (LIAC) or high (HIAC) inherent aerobic capacity were injected intraperitoneally with 1-methyl-1-nitrosurea (70 mg/kg body wt). At study termination 33 weeks post-carcinogen, cancer incidence (14.0 versus 47.3%; P < 0.001) and multiplicity (0.18 versus 0.85 cancers per rat; P < 0.0001) were significantly decreased in HIAC versus LIAC rats, respectively. HIAC had smaller visceral and subcutaneous body fat depots than LIAC and activity of two proteins that regulated the mammalian target of rapamycin, protein kinase B (Akt), and adenosine monophosphate-activated protein kinase were suppressed and activated, respectively, in HIAC. Although many factors distinguish between HIAC and LIAC, it appears that the protective effect of HIAC against breast carcinogenesis is mediated, at least in part, via alterations in core metabolic signaling pathways deregulated in the majority of human breast cancers.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgx066