Expression and function of fatty acid amide hydrolase in prostate cancer
Expression and function of fatty acid amide hydrolase in prostate cancer
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DOI：
10.1002/ijc.23674
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发表时间：
2008-09-15
影响因子：
6.4
通讯作者：
Nithipatikom, Kasem
中科院分区：
文献类型：
--
作者：
Endsley, Michael P.;Thill, Rebecca;Nithipatikom, Kasem
内源性大麻素的水解对内源性大麻素信号系统在前列腺癌细胞调节中的功能具有深远的影响。前列腺癌细胞对主要的内源性大麻素 2-花生四烯酰甘油 (2-AG) 表现出广泛的水解活性。然而，负责 2-AG 水解的酶及其在前列腺癌中的功能尚未得到表征。在这项研究中，我们证明脂肪酸酰胺水解酶（FAAH）在正常细胞和前列腺癌细胞中存在差异表达。在PC-3细胞中，FAAH的过度表达导致FAAH蛋白、2-AG水解、细胞侵袭和细胞迁移增加。相反，LNCaP 细胞中 FAAH 的小干扰 RNA (siRNA) 敲低会降低 FAAH 蛋白、2-AG 水解和细胞侵袭。此外，FAAH 抑制剂 CAY10401 可减少细胞侵袭，并增强 FAAH siRNA 转染的 LNCaP 细胞侵袭的减少。商业组织微阵列 (TMA) 的免疫组织化学染色显示，前列腺腺癌的 157 个核心中的 109 个具有 FAAH 染色，但正常前列腺组织的 8 个核心中的 I 染色较弱。这些结果表明，FAAH 调节 2-AG 水解和前列腺癌细胞的侵袭，并可能参与前列腺肿瘤发生。 (C) 2008 年威利利斯。公司
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 I 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. (C) 2008 Wiley-Liss. Inc.