MP29-15 MAKE IT FROM SCRATCH OR HAVE IT DELIVERED? SATISFYING THE FATTY ACID DEMAND OF PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2018MP29-15 MAKE IT FROM SCRATCH OR HAVE IT DELIVERED? SATISFYING THE FATTY ACID DEMAND OF PROSTATE CANCER Sandra Gaston, Soroush Rais-Bahrami, Jeffrey Nix, Peter Kolettis, James Bryant, James Kearns, Oelschlager Denise, Dennis Otali, and William Grizzle Sandra GastonSandra Gaston More articles by this author , Soroush Rais-BahramiSoroush Rais-Bahrami More articles by this author , Jeffrey NixJeffrey Nix More articles by this author , Peter KolettisPeter Kolettis More articles by this author , James BryantJames Bryant More articles by this author , James KearnsJames Kearns More articles by this author , Oelschlager DeniseOelschlager Denise More articles by this author , Dennis OtaliDennis Otali More articles by this author , and William GrizzleWilliam Grizzle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.935AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES One of the hallmarks of the malignant phenotype is an increase in the cell's demand for fatty acids (FA). Many cancers, including prostate cancer (PrCa), show increased expression of fatty acid synthase (FASN), a multi-component enzyme that catalyzes the de novo synthesis of the FA palmitate. However recent observations suggest that alternate mechanisms for FA acquisition are also important, including the utilization of exogenous palmitate when it's available. Recently, through a biopsy-based molecular analysis of high risk PrCa, we identified a tumor subtype with very high (>10 fold) "outlier" overexpression of fatty acid binding protein 5 (FABP5). FABP5 is involved in lipid transport and signaling, and it facilitates the utilization of palmitate and other FAs from outside of the cell. De novo palmitate synthesis by the FASN pathway is energetically expensive compared to utilization of exogenous FAs. We propose that PrCas that can efficiently utilizes exogenous palmitate are at a selective advantage when dietary FAs are abundant. In this study, to test that hypothesis, we compared FABP5 and FASN expression levels in PrCas obtained from diagnostic biopsies from normal weight, overweight and obese study subjects. METHODS A total of 201 consecutive eligible prostate biopsy patients were prospectively enrolled; 151 (75%) of these patients were cancer positive. PrCa FABP5 and FASN mRNA expression were measured by qrtPCR and FABP5/FASN and FASN/FABP5 expression ratios were determined for each cancer positive core. BMI and self-identified race were obtained from hospital records. RESULTS The expression of FABP5 and the FABP5/FASN expression ratio were significantly higher in overweight and obese individuals compared to normal weight individuals (mean FABP5/FASN overexpression ratio of 20.2 in overweight/obese subjects vs 4.0 in normal weight subjects; p < 0.05). The highest levels of PrCa FABP5 outlier overexpression (FABP5/FASN > 100) were observed in African American subjects with BMI > 30. CONCLUSIONS Our results are consistent with a growing body of evidence suggesting that the well-recognized "addiction" of PrCa for FA can be satisfied by more than one mechanism. In our study population, PrCa subtypes with high levels of FABP5 overexpression were more common in biopsy patients who were overweight or obese. Such FABP5 dominant PrCa subtypes may be more sensitive to dietary interventions than the more widely studied FASN dominant PrCas. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e371 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Sandra Gaston More articles by this author Soroush Rais-Bahrami More articles by this author Jeffrey Nix More articles by this author Peter Kolettis More articles by this author James Bryant More articles by this author James Kearns More articles by this author Oelschlager Denise More articles by this author Dennis Otali More articles by this author William Grizzle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...