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

Zhu, Y., Aupperlee, M.D., Zhao, Y., Tan, Y.S., Kirk, E.L., Sun, X., Troester, M.A., Schwartz, R.C. and Haslam, S.Z. (2016) Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis. Oncotarget, 7 (50). pp. 83409-83423.

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.

Item Type:	Journal Article
Publisher:	Impact Journals
URI:	http://researchrepository.murdoch.edu.au/id/eprint/65318

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