Androgen‐dependent regulation of medium and long chain fatty acids uptake in prostate cancer

AbstractBACKGROUNDEpidemiological and experimental studies suggest that both fatty acids and androgens have a role in the development and progression of prostate cancer (PC). Plasma membrane fatty acid binding protein (FABPpm) is a transporter of medium and long chain fatty acids (MCFA and LCFA) across the plasma membrane, and is identical to the mitochondrial protein aspartate aminotransferase (mAAT) that is regulated by testosterone only in prostate epithelial cells, a site where PC initially develops. We therefore hypothesized that FABPpm is also regulated by androgens.METHODSWe examined the effect of a synthetic androgen, R1881, and that of androgen receptor (AR) blocker, bicalutamide, on the expression of FABPpm and mAAT and on the uptake of fatty acids in the androgen‐sensitive LNCaP, androgen responsive 22rv1 and androgen‐independent CL1 human PC cells. This was done using immunofluorescence and confocal microscopy, Western blot, flow cytometry, and 3H‐oleate uptake studies.RESULTSAndrogen supplementation increased the cellular and surface expression of FABPpm and mAAT and increased the uptake of fluorescently labeled MCFA and LCFA and that of 3H‐oleate only in PC cells that express the AR. Bicalutamide inhibited this phenomenon.CONCLUSIONSThe uptake of MCFA and LCFA into PC cells is androgen regulated as well as the expression of FABPpm and mAAT. Prostate 67: 1330–1338, 2007. © 2007 Wiley‐Liss, Inc.

Androgen‐dependent regulation of medium and long chain fatty acids uptake in prostate cancer Journal Articles