Premium
The expression and functions of fatty acid amide hydrolase in prostate cancer
Author(s) -
Endsley Michael Patrick,
Isbell Marilyn A.,
Choudhry Iffat,
KajdacsyBalla Andre,
Campbell William B.,
Nithipatikom Kasem
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a421-b
Subject(s) - fatty acid amide hydrolase , lncap , endocannabinoid system , prostate cancer , cancer research , prostate , cannabinoid receptor , anandamide , biology , chemistry , medicine , cancer , biochemistry , receptor , antagonist
Endocannabinoid signaling system is comprised of cannabinoid receptors, endocannabinoids, and enzymes that synthesize and metabolize endocannabinoids. It has been implicated in the regulation of several cancers. 2‐Arachidonoylglycerol (2‐AG) is endogenously produced and inhibits invasion of prostate carcinoma cells. In response to inhibitors, 2‐AG concentrations, 2‐AG hydrolysis activities, and cell invasions are markedly different between 3 prostate carcinoma cell lines, PC‐3, DU‐145, and LNCaP. The aim of this study is to determine the expression and contribution of fatty acid amide hydrolase (FAAH) in the regulation of cell invasion. Western blot and RT‐PCR analysis indicated high levels of FAAH expression in LNCaP cells but very low in normal prostate epithelial and PC‐3 cells. Inhibition of FAAH by siRNA or inhibitors in LNCaP cells significantly decreased 2‐AG hydrolysis, increased endogenous 2‐AG concentration, and inhibited cell invasion. Immunohistochemistry staining for FAAH in prostate tumor tissue microarrays indicated low FAAH expression in normal tissues. FAAH is highly expressed in the low grades; however, it is decreased in the higher grades of prostate tumors. These results suggest that the expression of FAAH varies between cell lines and maybe associated with prostate tumor development. The inhibition of FAAH may be a novel approach for treatment of prostate cancer.