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Expression and function of fatty acid amide hydrolase in prostate cancer
Author(s) -
Endsley Michael P.,
Thill Rebecca,
Choudhry Iffat,
Williams Carol L.,
KajdacsyBalla Andre,
Campbell William B.,
Nithipatikom Kasem
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23674
Subject(s) - lncap , fatty acid amide hydrolase , endocannabinoid system , cancer research , prostate cancer , prostate , biology , carcinogenesis , chemistry , biochemistry , cancer , cannabinoid receptor , genetics , receptor , gene , agonist
Abstract 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. © 2008 Wiley‐Liss, Inc.