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Epac inhibits migration and proliferation of human prostate carcinoma cells
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 [(3)H]thymid...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795436/ https://www.ncbi.nlm.nih.gov/pubmed/19920825 http://dx.doi.org/10.1038/sj.bjc.6605439 |
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author | Grandoch, M Rose, A ter Braak, M Jendrossek, V Rübben, H Fischer, J W Schmidt, M Weber, A A |
author_facet | Grandoch, M Rose, A ter Braak, M Jendrossek, V Rübben, H Fischer, J W Schmidt, M Weber, A A |
author_sort | Grandoch, M |
collection | PubMed |
description | 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 [(3)H]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. |
format | Text |
id | pubmed-2795436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-27954362010-12-14 Epac inhibits migration and proliferation of human prostate carcinoma cells Grandoch, M Rose, A ter Braak, M Jendrossek, V Rübben, H Fischer, J W Schmidt, M Weber, A A Br J Cancer Short Communication 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 [(3)H]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. Nature Publishing Group 2009-12-15 2009-11-17 /pmc/articles/PMC2795436/ /pubmed/19920825 http://dx.doi.org/10.1038/sj.bjc.6605439 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Short Communication Grandoch, M Rose, A ter Braak, M Jendrossek, V Rübben, H Fischer, J W Schmidt, M Weber, A A Epac inhibits migration and proliferation of human prostate carcinoma cells |
title | Epac inhibits migration and proliferation of human prostate carcinoma cells |
title_full | Epac inhibits migration and proliferation of human prostate carcinoma cells |
title_fullStr | Epac inhibits migration and proliferation of human prostate carcinoma cells |
title_full_unstemmed | Epac inhibits migration and proliferation of human prostate carcinoma cells |
title_short | Epac inhibits migration and proliferation of human prostate carcinoma cells |
title_sort | epac inhibits migration and proliferation of human prostate carcinoma cells |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795436/ https://www.ncbi.nlm.nih.gov/pubmed/19920825 http://dx.doi.org/10.1038/sj.bjc.6605439 |
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