Epac inhibits migration and proliferation of human prostate carcinoma cells

被引：50
|
作者：
Grandoch, M. [1 ]
Rose, A. [1 ,2 ]
ter Braak, M. [1 ]
Jendrossek, V. [2 ]
Ruebben, H. [3 ]
Fischer, J. W. [1 ]
Schmidt, M. [4 ]
Weber, A. A. [1 ]
机构：
[1] Univ Essen Gesamthsch, Sch Med, Dept Pharmacol, Essen, Germany
[2] Univ Duisburg Essen, Dept Mol Cell Biol, Inst Cell Biol, Essen, Germany
[3] Univ Essen Gesamthsch, Sch Med, Dept Urol & Urooncol, Essen, Germany
[4] Univ Groningen, Dept Mol Pharmacol, Groningen, Netherlands
来源：
BRITISH JOURNAL OF CANCER | 2009年 / 101卷 / 12期
关键词：
prostate cancer; cAMP; Epac; PROTEIN-KINASE; ACTIVATION; DIFFERENTIATION; EXPRESSION;
D O I：
10.1038/sj.bjc.6605439
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [H-3] thymidine incorporation and scratch assays in PC-3 and DU 145 cells. Furthermore, cytoskeletal integrity was analysed by phalloidin staining. The participation of intracellular Epac effectors such as mitogen-activated protein (MAP) kinases, Rap1- and Rho-GTPases was determined by immunoblotting and pull-down assay. RESULTS: The specific Epac activator 8-pCPT-2'-O-Me-cAMP (8-pCPT) interfered with cytoskeletal integrity, reduced DNA synthesis, and migration. Although 8-pCPT activated Rap1, it inhibited MAP kinase signalling and RhoA activation. These findings were translated into functional effects such as inhibition of mitogenesis, cytoskeletal integrity, and migration. CONCLUSION: In human prostate carcinoma cells, Epac inhibits proliferative and migratory responses likely because of inhibition of MAP kinase and RhoA signalling pathways. Therefore, Epac might represent an attractive therapeutic target in the treatment of prostate cancer. British Journal of Cancer (2009) 101, 2038-2042. doi: 10.1038/sj.bjc.6605439 www.bjcancer.com Published online 17 November 2009 (C) 2009 Cancer Research UK
引用
收藏
页码：2038 / 2042
页数：5
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