| Inhibition of Rho-Kinase Abrogates Migration of Human Transitional Cell Carcinoma Cells: Results of an in vitro Study. | |
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MedLine Citation:
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PMID: 21051874 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Introduction: Migration of cells involves a complex signaling network. The aim of the present study was to elucidate the impact of Rho-kinase (ROK) on G protein-coupled receptor-induced migration of human transitional cell carcinoma cells in an in vitro experimental setting. Materials and Methods: Intracellular calcium concentration ([Ca(2+)](i)) was measured with the indicator dye Fura-2 in response to lysophosphatidic acid, thrombin and sphingosine-1-phosphate. Phospholipase C activity was determined in myo-[(3)H]inositol- (0.5 μCi/ml) labeled cells. Migration was performed using a Boyden chamber. Transient transfection of a dominant-negative mutant of ROK was done with calcium phosphate. For staining of actin filaments, tetramethylrhodamine isothiocyanate-conjugated phalloidin was used. Results: Lysophosphatidic acid, thrombin and sphingosine-1-phosphate cause increases in [Ca(2+)](i), cellular responses being accompanied by an enhancement of phospholipase C activity and sensitive to the G(i) inhibitor pertussis toxin. Agonists potently stimulated migration of T24 and J82 cells. Inhibition of Rho proteins by Clostridium difficile toxin B abrogated cell migration. Inhibition of ROK using HA1077 and Y-27632 mimicked the properties of toxin B. Expression of a ROK mutant drastically reduced migration. Conclusions: G protein-coupled receptors potently stimulated cell migration in T24 and J82 cells. Rho proteins and ROK play a pivotal role in this signaling cascade. Rho and ROK may be putative targets for new therapy options in bladder cancer. |
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Authors:
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Frank Vom Dorp; Harald Sanders; Christof Boergermann; Gerd Lümmen; Herbert Rübben; Karl H Jakobs; Martina Schmidt |
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Publication Detail:
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Type: Journal Article Date: 2010-11-04 |
Journal Detail:
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Title: Urologia internationalis Volume: 86 ISSN: 1423-0399 ISO Abbreviation: Urol. Int. Publication Date: 2011 |
Date Detail:
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Created Date: 2011-03-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0417373 Medline TA: Urol Int Country: Switzerland |
Other Details:
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Languages: eng Pagination: 220-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 S. Karger AG, Basel. |
Affiliation:
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Institute for Pharmacology, University of Essen Medical School, Essen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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