Document Detail


Differential role of Sloan-Kettering Institute (Ski) protein in Nodal and transforming growth factor-beta (TGF-β)-induced Smad signaling in prostate cancer cells.
MedLine Citation:
PMID:  22843506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and tumor promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, and its receptors are expressed in prostate cancer cells. Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1 and DU145 cells, whereas neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-β induced migration in PC3 cells, but not in DU145 cells. TGF-β induced predominantly phosphorylation of Smad3, whereas Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a corepressor of Smad2/3, in Nodal and TGF-β signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF-β had no effects on Ski mRNA levels. On the other hand, TGF-β induced a rapid degradation of Ski protein mediated by the proteasomal pathway, whereas Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad3 signaling, but Ski protein levels do not influence Nodal and Smad2 signaling.
Authors:
BaoHan T Vo; Bianca Cody; Yang Cao; Shafiq A Khan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-07-27
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-30     Completed Date:  2013-01-17     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  2054-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Movement
Cell Proliferation
Cells, Cultured
DNA-Binding Proteins / antagonists & inhibitors,  genetics,  metabolism*
Fluorescent Antibody Technique
Humans
Immunoprecipitation
Male
Nodal Protein / genetics,  metabolism*
Phosphorylation
Prostate / metabolism*,  pathology
Prostatic Neoplasms / metabolism*
Protein Binding
Proto-Oncogene Proteins / antagonists & inhibitors,  genetics,  metabolism*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Smad2 Protein / genetics,  metabolism*
Smad3 Protein / genetics,  metabolism*
Transforming Growth Factor beta / genetics,  metabolism*
Wound Healing
Grant Support
ID/Acronym/Agency:
2G12RR003062/RR/NCRR NIH HHS; 2R25GM060414/GM/NIGMS NIH HHS; 5P20MD002285-02/MD/NIMHD NIH HHS; G12 RR003062/RR/NCRR NIH HHS; P20 MD002285/MD/NIMHD NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/NODAL protein, human; 0/Nodal Protein; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/Smad2 Protein; 0/Smad3 Protein; 0/Transforming Growth Factor beta; 126648-96-2/SKI protein, human
Comments/Corrections

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