Expression and function of fatty acid amide hydrolase in prostate cancer.
The hydrolysis of endocannabinoids has profound effects on the function of the endocannabinoid signaling system in the regulation of prostate carcinoma cells. Prostate carcinoma cells exhibit a wide range of hydrolysis activity for 2-arachidonoylglycerol (2-AG), the major endocannabinoid. However, enzyme(s) responsible for 2-AG hydrolysis and their functions in prostate cancer have not been characterized. In this study, we demonstrated that fatty acid amide hydrolase (FAAH) was differentially expressed in normal and prostate carcinoma cells. In PC-3 cells, overexpression of FAAH resulted in increased FAAH protein, 2-AG hydrolysis, cell invasion and cell migration. Conversely, small-interfering RNA (siRNA) knockdown of FAAH in LNCaP cells decreased FAAH protein, 2-AG hydrolysis and cell invasion. Furthermore, CAY10401, a FAAH inhibitor, decreased cell invasion and it enhanced the reduction of invasion in FAAH siRNA-transfected LNCaP cells. Immunohistochemistry staining of commercial tissue microarrays (TMAs) demonstrated FAAH staining in 109 of 157 cores of prostate adenocarcinomas but weak staining in 1 of 8 cores of normal prostate tissues. These results suggest that FAAH regulates 2-AG hydrolysis and invasion of prostate carcinoma cells and is potentially involved in prostate tumorigenesis.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Michael P
MP
Endsley
Rebecca
R
Thill
Iffat
I
Choudhry
Carol L
CL
Williams
Andre
A
Kajdacsy-Balla
William B
WB
Campbell
Kasem
K
Nithipatikom
D000230:Adenocarcinoma / Q000201:enzymology*; D000581:Amidohydrolases / Q000096:biosynthesis* / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002853:Chromatography, Liquid; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D046888:Tissue Array Analysis; D014162:Transfection; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D034741:RNA, Small Interfering; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate