Document Detail

Gli2 expression and human bladder transitional carcinoma cell invasiveness.
MedLine Citation:
PMID:  20488474     Owner:  NLM     Status:  MEDLINE    
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.
Clay W Mechlin; Matthew J Tanner; Mengqian Chen; Ralph Buttyan; Robert M Levin; Badar M Mian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-20
Journal Detail:
Title:  The Journal of urology     Volume:  184     ISSN:  1527-3792     ISO Abbreviation:  J. Urol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-07-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  344-51     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Division of Urology, Albany Medical College, Albany, New York, USA.
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MeSH Terms
Blotting, Western
Carcinoma, Transitional Cell / genetics*
Cell Line, Tumor
Dioxoles / pharmacology
Gene Expression Profiling
Hedgehog Proteins / antagonists & inhibitors,  genetics*
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
Reg. No./Substance:
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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