Document Detail

Molecular determinants of cell death induction following adenovirus-mediated gene transfer of wild-type p53 in prostate cancer cells.
MedLine Citation:
PMID:  11146439     Owner:  NLM     Status:  MEDLINE    
Adenoviral vectors expressing wild-type p53 (Ad-p53) induce apoptosis in different types of cancer cells. The therapeutic utility of Ad-p53 is now being evaluated in prostate-cancer patients. Bcl-2 is frequently expressed by prostate-cancer cells and has previously been shown to inhibit p53-mediated cell death following genotoxic stress. We studied the impact of bcl-2 on Ad-p53-induced cell death in human prostate-cancer cells. Human prostate-cancer cell lines LNCaP (p53 wt) and PC3 (p53 mut) were stably transfected with bcl-2. After p53 transduction, cell viability, apoptosis induction and modulation of specific apoptosis-regulatory proteins were assessed. LNCaP vector control and bcl-2-expressing cells underwent similar decreases in viability associated with apoptosis induction following Ad-p53 infection. Increased bcl-2 expression provided significant protection to PC3 cells transduced with Ad-p53. These findings are correlated with modulations in bax, bcl-2, bcl-x(L) and p21 protein levels. These data suggest that Ad-p53 may be useful in the treatment of some prostate cancers.
G Schumacher; E M Bruckheimer; A W Beham; T Honda; S Brisbay; J A Roth; C Logothetis; T J McDonnell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  91     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-02     Completed Date:  2001-02-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  159-66     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
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MeSH Terms
Adenoviridae / genetics*
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / physiology
Gene Therapy*
Genes, p53*
Prostatic Neoplasms / pathology,  therapy*
Proto-Oncogene Proteins c-bcl-2 / analysis
Tumor Cells, Cultured
Grant Support
P01 CA78778/CA/NCI NIH HHS; T32 CA67759-01/CA/NCI NIH HHS
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Proto-Oncogene Proteins c-bcl-2

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