Androgen-dependent regulation of medium and long chain fatty acids uptake in prostate cancer.
BACKGROUND
Epidemiological 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 (FABP(pm)) 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 FABP(pm) is also regulated by androgens.


METHODS
We examined the effect of a synthetic androgen, R1881, and that of androgen receptor (AR) blocker, bicalutamide, on the expression of FABP(pm) 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 (3)H-oleate uptake studies.


RESULTS
Androgen supplementation increased the cellular and surface expression of FABP(pm) and mAAT and increased the uptake of fluorescently labeled MCFA and LCFA and that of (3)H-oleate only in PC cells that express the AR. Bicalutamide inhibited this phenomenon.


CONCLUSIONS
The uptake of MCFA and LCFA into PC cells is androgen regulated as well as the expression of FABP(pm) and mAAT.
Pinthus
Jehonathan H
JH
Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
Lu
Jian-Ping
JP
Bidaisee
Laure A
LA
Lin
Helen
H
Bryskine
Inna
I
Gupta
Radhey S
RS
Singh
Gurmit
G
D000230:Adenocarcinoma / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D024442:Aspartate Aminotransferase, Mitochondrial / Q000096:biosynthesis / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000493:pharmacokinetics; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D018613:Microscopy, Confocal; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology; D015854:Up-Regulation
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009570:Nitriles; D014105:Tosyl Compounds; D015741:Metribolone; D019301:Oleic Acid; C053541:bicalutamide; D024442:Aspartate Aminotransferase, Mitochondrial