Abstract 4315: Effects of increased dietary fat consumption on prostate cancer progression in genetically engineered mice

Abstract

Abstract Prostate cancer is a highly heterogeneous disease and evidence indicates that lifestyle and environmental factors can contribute to cancer-related deaths. Accumulating data also suggests that increased dietary fat consumption may promote and increase the risk of prostate cancer-related morbidity and mortality. However, data between studies is inconsistent and a direct link between increased consumption of dietary fat and the promotion of prostate cancer remains unclear. Here, we present our findings from a preclinical study of increased dietary fat consumption and its effects on prostate tumor growth and progression using genetically engineered mouse models of prostate cancer. We determined the effects of a high fat diet on tumor cell proliferation and apoptosis in vivo using a well-established mouse model of prostate cancer. Twenty-week-old mice, with conditional biallelic deletion of PTEN, harboring castration-naïve or castration-resistant prostate tumors were randomized and assigned to a standard laboratory diet (4% fat) or a high-fat diet (HFD, 13.6% fat) for 8 weeks. In both tumor models, mice fed a HFD had increased expression levels of proteins associated with proliferation and decreased levels of apoptosis markers. To determine the long term effects of a HFD, we used a mouse model of advanced prostate cancer. Mice with concomitant inactivation of PTEN and p53 develop tumors that progress quickly and are characterized with increased metastatic development and decreased survival compared to PTEN knockout mice. PTEN/p53 double knockout mice were randomized and assigned to control or HFD experimental groups after weaning. Our findings revealed that mice fed a HFD resulted in obesity that led to decreased progression-free survival and overall survival rates compared to mice fed a standard diet. Our results provide evidence to support the effects of high dietary fat consumption and increased prostate cancer risk, and provide a platform to investigate chemoprevention strategies. Citation Format: Marco A. De Velasco, Yurie Kura, Yuji Hatanaka, Takashi Oki, Yutaka Yamamoto, Koichi Sugimoto, Yasunori Mori, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Effects of increased dietary fat consumption on prostate cancer progression in genetically engineered mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4315.