Document Detail


BBC3 mediates fenretinide-induced cell death in neuroblastoma.
MedLine Citation:
PMID:  16091745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fenretinide (4-HPR) is a synthetic retinoid whose apoptosis-inducing effects have been demonstrated in many tumor types. The precise mechanism of its apoptotic action is not fully understood. To further study the mechanism by which 4-HPR exerts its biological effects in neuroblastoma (NB) and to identify the genes that contribute to the induction of apoptosis, we determined the sensitivity of eight NB cell lines to 4-HPR. Additionally, cDNA microarray analysis was performed on a 4-HPR-sensitive cell line to investigate the temporal changes in gene expression, primarily focusing on the induction of proapoptotic genes. BBC3, a transcriptionally regulated proapoptotic member of the BCL2 family, was the most highly induced proapoptotic gene. Western analysis confirmed the induction of BBC3 protein by 4-HPR. Furthermore, the induction of BBC3 was associated with the sensitivity to this agent in the cell lines tested. Finally we demonstrated that BBC3 alone is sufficient to induce cell death in the 4-HPR-sensitive and resistant NB cell lines, and that siRNA against BBC3 significantly decreases apoptosis induced by 4-HPR. Our results indicate that BBC3 mediates cell death in NB cells in response to 4-HPR.
Authors:
Jun S Wei; Craig C Whiteford; Nicola Cenacchi; Chang Gue Son; Javed Khan
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-02     Completed Date:  2005-12-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  7976-83     Citation Subset:  IM    
Affiliation:
Pediatric Oncology Branch, National Cancer Institute, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis Regulatory Proteins / metabolism*
Blotting, Western
Cell Division / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Colorimetry
DNA, Complementary
DNA, Neoplasm / analysis
Fenretinide / pharmacology*
Flow Cytometry
Gene Expression Regulation, Neoplastic / drug effects
Humans
Kinetics
Microarray Analysis
Neoplasm Proteins / biosynthesis,  genetics,  physiology*
Neuroblastoma / drug therapy*,  genetics,  metabolism,  pathology
Proto-Oncogene Proteins / metabolism*
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation / drug effects
Grant Support
ID/Acronym/Agency:
Z01 BC010594-02/BC/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/BBC3 protein, human; 0/DNA, Complementary; 0/DNA, Neoplasm; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 65646-68-6/Fenretinide
Comments/Corrections

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