Oncotarget

Research Papers:

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

Yirong Zhu, Mark D. Aupperlee, Yong Zhao, Ying Siow Tan, Erin L. Kirk, Xuezheng Sun, Melissa A. Troester, Richard C. Schwartz and Sandra Z. Haslam _

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Oncotarget. 2016; 7:83409-83423. https://doi.org/10.18632/oncotarget.13112

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Abstract

Yirong Zhu1, Mark D. Aupperlee2, Yong Zhao2, Ying Siow Tan2, Erin L. Kirk4, Xuezheng Sun4, Melissa A. Troester4,5,6, Richard C. Schwartz3, Sandra Z. Haslam2

1Cell and Molecular Biology Program and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA

2Department of Physiology and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA

3Department of Microbiology and Molecular Genetics and Breast Cancer and the Environment Research Program, Michigan State University, East Lansing, MI, USA

4Department of Epidemiology, University of North Carolina at Chapel Hill, NC, USA

5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA

6Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA

Correspondence to:

Sandra Z. Haslam, email: shaslam@msu.edu

Richard C. Schwartz, email: schwart9@msu.edu

Keywords: dietary animal fat, breast cancer, puberty, adulthood, Trp53-null

Received: July 22, 2016     Accepted: October 19, 2016     Published: November 04, 2016

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.


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