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Oncotarget. 2016 Dec 13;7(50):83409-83423. doi: 10.18632/oncotarget.13112.

Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis.

Author information

1
Cell and Molecular Biology Program and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA.
2
Department of Physiology and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA.
3
Department of Epidemiology, University of North Carolina at Chapel Hill, NC, USA.
4
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA.
5
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.
6
Department of Microbiology and Molecular Genetics and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA.

Abstract

Premenopausal breast cancer is associated with increased animal fat consumption among normal weight, but not overweight women (Farvid et al., 2014). Our previous findings in obesity-resistant BALB/c mice similarly showed promotion of carcinogen-induced mammary tumorigenesis by a diet high in saturated animal fat (HFD). This effect was specific to pubertal versus adult HFD. This study identifies the effects of HFD during puberty versus adulthood in Trp53-null transplant BALB/c mice and investigates its mechanism of enhancing tumorigenesis. Either pubertal or adult HFD is sufficient to increase incidence of Trp53-null mammary tumors. Puberty-restricted HFD exposure promoted tumor cell proliferation, increased angiogenesis, and increased recruitment of total and M2 macrophages in epithelial tumors. Adult-restricted exposure to HFD similarly increased proliferation, angiogenesis, recruitment of total and M2 macrophages, and additionally reduced apoptosis. Adult HFD also increased incidence of spindle cell carcinomas resembling claudin-low breast cancer, and thus adult HFD in the Trp53-null transplantation system may be a useful model for human claudin low breast cancer. Importantly, these results on Trp53-null and our prior studies on DMBA-induced mammary tumorigenesis demonstrate a pubertal window of susceptibility to the promotional effects of HFD, indicating the potential of early life dietary intervention to reduce breast cancer risk.

KEYWORDS:

Trp53-null; adulthood; breast cancer; dietary animal fat; puberty

PMID:
27825136
PMCID:
PMC5347778
DOI:
10.18632/oncotarget.13112
[Indexed for MEDLINE]
Free PMC Article

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