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

Y. Zhu; M.D. Aupperlee; Y. Zhao; Y.S. Tan; E.L. Kirk; X. Sun; M.A. Troester; R.C. Schwartz; S.Z. Haslam

doi:10.18632/oncotarget.13112

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

Journal article

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Peer reviewed

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

Y. Zhu, M.D. Aupperlee, Y. Zhao, Y.S. Tan, E.L. Kirk, X. Sun, M.A. Troester, R.C. Schwartz and S.Z. Haslam

Oncotarget, Vol.7(50), pp.83409-83423

2016

DOI: https://doi.org/10.18632/oncotarget.13112

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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.

Details

Title: Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis
Authors/Creators: Y. Zhu (Author/Creator) - Michigan State University
M.D. Aupperlee (Author/Creator) - Michigan State University
Y. Zhao (Author/Creator) - Michigan State University
Y.S. Tan (Author/Creator) - Michigan State University
E.L. Kirk (Author/Creator) - University of North Carolina at Chapel Hill
X. Sun (Author/Creator) - University of North Carolina at Chapel Hill
M.A. Troester (Author/Creator) - University of North Carolina at Chapel Hill
R.C. Schwartz (Author/Creator) - Michigan State University
S.Z. Haslam (Author/Creator) - Michigan State University
Publication Details: Oncotarget, Vol.7(50), pp.83409-83423
Publisher: Impact Journals
Identifiers: 991005541654007891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.119 Breast Cancer Scanning; 1.119.454 Screening Disparities
Web Of Science research areas: Cell Biology; Oncology
ESI research areas: Molecular Biology & Genetics