MP31-06 DIET INDUCED ALTERATION OF FATTY ACID SYNTHASE IS INVOLVED IN PROSTATE CANCER PROGRESSION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2014MP31-06 DIET INDUCED ALTERATION OF FATTY ACID SYNTHASE IS INVOLVED IN PROSTATE CANCER PROGRESSION Mingguo Huang, Shintaro Narita, Norihiko Tsuchiya, Takamitsu Inoue, Shigeru Satoh, Hiroshi Nanjo, Takehiko Sasaki, and Tomonori Habuchi Mingguo HuangMingguo Huang More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Hiroshi NanjoHiroshi Nanjo More articles by this author , Takehiko SasakiTakehiko Sasaki More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.915AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High-fat diet (HFD) or obesity is strongly suggested to influence prostate cancer (PCa) progression, but the underlying mechanism is not well defined. Fatty acid synthase (FASN) is a cytosolic metabolic enzyme catalyzing de novo biosynthesis of fatty acid. METHODS In the present study, we investigated the role of FASN on PCa progression in the LNCaP xenograft mouse fed HFD or low-fat diet (LFD). RESULTS The tumor growth was increased in the HFD group than LFD group (p = 0.025). The mRNA expression of FASN and SREBP-1, which encodes Sterol regulatory element-binding protein-1 (SREBP-1) were increased in the xenograft tumor by 1.8- and 2.1-fold, respectively (p < 0.05). The serum level of FASN was significantly lower in the HFD group than in the LFD group (p = 0.026) and correlated inversely with the tumor volumes (total, r = 0.642, p = 0.022; HFD group, r = −0.618, p = 0.024; LFD group, r = −0.439, p = 0.154; respectively). Upregulation of P-AKT and P-ERK, and downregulation of P-AMPK were observed in xenograft tumors of the HFD group than LFD group. The extracellular release of FASN protein in vitro and AMPK activation was induced in the PCa cells by inhibition of the PI3K and MAPK signaling. In addition, pharmacological activation of AMPK stimulated the extracellular FASN release along with the downregulation of FASN and SREBP-1 in the PCa cells in dose-dependent manner. Cell proliferation was significantly decreased in the PCa cells by inhibition of FASN, and the decreased effect was rescued by addition of palmitic acid. Clinically, imuunohistological evaluation of surgical specimens showed that the expression of FASN was markedly decreased in the PCa response to hormone and chemotherapy. CONCLUSIONS In conclusion, HFD increased the FASN expression and inhibited the extracellular release of FASN, which may be one of important mechanism in HFD or obesity associated PCa progression. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e324 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mingguo Huang More articles by this author Shintaro Narita More articles by this author Norihiko Tsuchiya More articles by this author Takamitsu Inoue More articles by this author Shigeru Satoh More articles by this author Hiroshi Nanjo More articles by this author Takehiko Sasaki More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...