| Gli2 expression and human bladder transitional carcinoma cell invasiveness. | |
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MedLine Citation:
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PMID: 20488474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Hedgehog signaling regulates Gli transcription factors. Aberrant hedgehog signaling can be oncogenic and drugs that block hedgehog are being tested as anticancer agents. We considered whether hedgehog/Gli signaling may be involved in human bladder transitional cell carcinoma proliferative or invasive behavior. MATERIALS AND METHODS: We stratified the human bladder transitional cell carcinoma lines RT4 (ATCC), 253JP, 253BV, UMUC6 and UMUC3 for relative growth rate by cell counting and for in vitro invasiveness by Matrigel invasion assay. Cells were tested for growth inhibition by the hedgehog blocking drug cyclopamine or the inactive mimic tomatidine. Cell RNA was characterized for hedgehog signaling component expression, including ligands, receptors and signaling mediators, by quantitative reverse transcriptase-polymerase chain reaction. Gli2 expression or activity was modified by Gli2 expression lentiviruses or the Gli inhibitor GANT61. We measured effects on proliferation and invasiveness. RESULTS: Cell growth rates and invasiveness were stratified into an equivalent order (RT4 <243JP <253BV <UMUC6 <UMUC3). All cells were weakly growth inhibited by tomatidine and cyclopamine. Gli2 was the only hedgehog signaling molecule of which expression correlated with stratification. Manipulation of Gli2 expression or activity significantly affected cell invasiveness. CONCLUSIONS: Weak growth suppression by cyclopamine suggests that hedgehog signaling is not involved in bladder cancer cell proliferation but Gli2 expression strongly correlated with invasive behavior. Increased Gli2 expression increased low Gli2 cell invasiveness while Gli inhibition by GANT61 decreased high Gli2 cell invasiveness. Results suggest that Gli2 expression by noncanonical signaling contributes to bladder cancer cell invasiveness. |
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Authors:
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Clay W Mechlin; Matthew J Tanner; Mengqian Chen; Ralph Buttyan; Robert M Levin; Badar M Mian |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-20 |
Journal Detail:
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Title: The Journal of urology Volume: 184 ISSN: 1527-3792 ISO Abbreviation: J. Urol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-07-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376374 Medline TA: J Urol Country: United States |
Other Details:
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Languages: eng Pagination: 344-51 Citation Subset: AIM; IM |
Copyright Information:
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Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Urology, Albany Medical College, Albany, New York, USA. mianb@mail.amc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Carcinoma, Transitional Cell / genetics* Cell Line, Tumor Dioxoles / pharmacology Gene Expression Profiling Hedgehog Proteins / antagonists & inhibitors, genetics* Humans Kruppel-Like Transcription Factors / genetics* Linear Models Neoplasm Invasiveness / genetics* Nuclear Proteins / genetics* Piperazines / pharmacology Pyridines / pharmacology Pyrimidines / pharmacology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics* Tomatine / analogs & derivatives, pharmacology Urinary Bladder Neoplasms / genetics* Veratrum Alkaloids / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/CUR 61414; 0/Dioxoles; 0/GANT 61; 0/GLI2 protein, human; 0/Hedgehog Proteins; 0/Kruppel-Like Transcription Factors; 0/Nuclear Proteins; 0/Piperazines; 0/Pyridines; 0/Pyrimidines; 0/Veratrum Alkaloids; 17406-45-0/Tomatine; 4449-51-8/cyclopamine; 77-59-8/tomatidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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