Faculty Collaboration Database

Expression and function of fatty acid amide hydrolase in prostate cancer. Int J Cancer 2008 Sep 15;123(6):1318-26

Date

06/21/2008

Pubmed ID

18566995

Pubmed Central ID

PMC2548421

DOI

10.1002/ijc.23674

Scopus ID

2-s2.0-49749120682 (requires institutional sign-in at Scopus site)   82 Citations

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.

Author List

Endsley MP, Thill R, Choudhry I, Williams CL, Kajdacsy-Balla A, Campbell WB, Nithipatikom K

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Amidohydrolases
Arachidonic Acids
Blotting, Western
Cell Movement
Chromatography, Liquid
Endocannabinoids
Enzyme Inhibitors
Gene Expression
Glycerides
Humans
Immunohistochemistry
Male
Prostatic Neoplasms
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Mass, Electrospray Ionization
Tissue Array Analysis
Transfection