Document Detail


BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells.
MedLine Citation:
PMID:  20428771     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pathologically, >90% of bladder cancer is transitional cell carcinoma (TCC). Previously, brain-derived neurotrophic factor (BDNF) but not tropomyosin-related kinase B (TrkB) was found in normal urothelium. TrkB activation by BDNF has been shown to promote the progression of several cancers, however, the existence and functional roles of both BDNF and TrkB in TCC have not been elucidated. In this study, three human TCC cell lines, BFTC905, TSGH8301, and T24 were used for the investigation. Both BDNF and TrkB but not TrkA or TrkC identified by RT-PCR and Western blotting were found in these cell lines. Immunostaining demonstrated the cytosolic expression of BDNF and TrkB, as well as membranous expression of TrkB in these cells. BDNF released from three cell lines was also detected in culture medium by ELISA. The proliferation of BFTC905 cells was enhanced by recombinant human BDNF (rhBDNF) in vitro, which was associated with increased phospho-TrkB and phospho-ERK levels. In contrast, TrkB-Fc chimeric protein served as BDNF scavenger eliciting cytotoxicity. Addition of rhBDNF in these cell lines cultured in poly-HEMA [Poly(2-hydroxyethyl methacrylate)] coated dishes for 48 h did not confer resistance to anoikis. Increased phospho-Akt expression was observed transiently within an hour after rhBDNF administration but disappeared 24 h later. Weekly injections of 100 ng rhBDNF into the cancer cell-loading site for 6 weeks promoted BFTC905 xenograft growth in SCID mice. Daily injection of 5 microg TrkB-Fc chimeric protein into the tumor 2 weeks after tumor cell implantation delayed tumor growth concomitant with phospho-TrkB suppression in xenografts. These results indicate that BDNF binding to TrkB receptor is a survival signal for TCC cells. Drugs that block BDNF or TrkB may provide a new and potential approach for TCC therapy.
Authors:
Yen Ta Huang; Pei Chun Lai; Chia Chen Wu; Shih Hsin Hsu; Chuan Chu Cheng; Yi Fan Lan; Ted H Chiu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  36     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-29     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1469-76     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoikis / physiology
Blotting, Western
Brain-Derived Neurotrophic Factor / genetics,  metabolism*
Carcinoma, Transitional Cell / genetics,  metabolism*,  pathology
Cell Line, Tumor
Cell Proliferation
Cell Survival / physiology
Enzyme Activation / physiology*
Enzyme-Linked Immunosorbent Assay
Gene Expression
Gene Expression Profiling
Humans
Immunohistochemistry
Mice
Mice, SCID
Receptor, trkB / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology
Urinary Bladder Neoplasms / genetics,  metabolism*,  pathology
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; EC 2.7.10.1/Receptor, trkB

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