Document Detail


Expression of anti-apoptosis genes determines the response of adrenal cancer to apoptosis-inducing chemotherapy.
MedLine Citation:
PMID:  21187456     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes.
MATERIALS AND METHODS: Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera.
RESULTS: Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression.
CONCLUSION: This study provided proof of concept that expression of Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.
Authors:
David E Schteingart; Ricardo Benitez; Carol Bradford; Ajita Narayan; Shaomeng Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-28     Completed Date:  2011-02-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4805-9     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Rm 5570, MSRB 2, 1150 West Medical Center Dr, Ann Arbor MI 48109, USA. dschtein@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenal Cortex Neoplasms / drug therapy*,  genetics*,  metabolism,  pathology
Animals
Apoptosis / drug effects*,  genetics*
Cell Line, Tumor
Genes, bcl-2
Gossypol / pharmacology
Humans
Mice
Mice, SCID
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*,  genetics
Taxoids / pharmacology
bcl-X Protein / biosynthesis*,  genetics
Chemical
Reg. No./Substance:
0/BCL2L1 protein, human; 0/Proto-Oncogene Proteins c-bcl-2; 0/Taxoids; 0/bcl-X Protein; 15H5577CQD/docetaxel; 303-45-7/Gossypol

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