Abstract 843: Increased consumption of dietary fat contributes to increased prostate cancer-specific mortality in a transgenic mouse model of prostate cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 843
• Main Authors: Hatanaka, Yuji, De Velasco, Marco A., Tanaka, Motoyoshi, Doi, Makiko, Okazaki, Erina, Izumi, Ayaka, Yamamoto, Yutaka, Shimizu, Nobutaka, Yoshimura, Kazuhiro, Nozawa, Masahiro, Yoshikawa, Kazuhiro, Nishio, Kazuto, Uemura, Hirotsugu
• Format: Journal Article
• Language: English
• Published: 15.04.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-843

Abstract Purpose: Prostate cancer (PCa) is the most common tumor in men in western countries and represents the second leading cause of cancer related death. Large geographic variation in prostate cancer risk suggests that lifestyle factors, such as westernization, may also contribute to the etiology of this disease. Although results from large clinical studies have shown inconsistent findings with regards to obesity and prostate cancer-related mortality, increasing evidence has suggested a link between obesity and an increase in prostate cancer-specific mortality. Obesity is associated with an increased risk and worsened prognosis for many types of cancer, but the mechanisms underlying the obesity-cancer progression link are poorly understood. In our study we used the transgenic PSACre;PtenloxP/loxP mouse prostate tumor model, in combination with dietary and pharmacologic approaches to determine the role that a high fat diet has on the prostate carcinogenesis process. Methods: Thirty 6-week-old homozygous PSACre;PtenloxP/loxP mice were randomized and divided into normal diet (CE-2, 4% vegetable fat) or high-fat diet (Quick Fat, 13.6% animal plus N-nitroso-N-methylurea (NMU) 12.5mg/kg × 8 weeks) groups. Mice were kept on their respective diet until 75 weeks of age. Bodyweight, survival and tumor burden and histopathology was assessed in these mice. Putative molecular mechanisms involved in the progression of prostate cancer were determined by immunohistochemical methods. Results: At 75 weeks, average body weights were 33.2 +/- 1.3 and 36.7 +/- 2.14 grams for control and high-fat groups, respectively (p=0.16). However, mice fed the high-fat diet gained weight at a significantly faster rate up to 50 weeks of age (p<0.01), at which point body their weights began to decreased and plateau at 70 weeks. All mice fed the control diet were alive at the end of the experiment compared to 40% (6/15) survival in the high-fat diet group. Genitourinary tracts were weighed to assess PCa burden and weights were significantly higher in control mice compared to the high-fat group ((p=0.018). Interestingly, we observed significantly multiple metastatic rates in the high-fat group compared to controls, 64.2% vs. 76.9%, p<0.023, respectively. Histopathological analysis showed similar expression of expression of vimentin staining in tumors from both groups, however, tumors from mice in the high-fat group showed decreased expression of e-cadherin. Conclusion: The results from this study suggest that a high fat diet may contribute to increased PCa progression resulting in increased mortality. The mechanism involved may involve pathways that regulate e-cadherin expression such as epithelial mesenchymal transition (EMT). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 843. doi:10.1158/1538-7445.AM2011-843