Document Detail


Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells.
MedLine Citation:
PMID:  20554106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this work is to study mechanisms underlying anti-tumor effects of farnesyltransferase inhibitors (FTIs) in non-small cell lung cancer (NSCLC). We demonstrate that mRNA and protein levels of Ras homologue enriched in brain (Rheb) are highly expressed both in NSCLC tissues and in NSCLC cell lines. Rheb expression levels correlate with phosphorylation of its downstream target S6 and the sensitivity of NSCLC cells to FTIs (R115777 and SCH66336)-induced growth inhibition and apoptosis. FTIs effectively and preferentially inhibited Rheb downstream signaling in NSCLC cells. Moreover, inhibition of Rheb functions by FTIs or dominant-negative Rheb mutants enhance the effects of cisplatin on NSCLC cells. Rheb-CSVL, a FTIs-resistant mutant, reduces the effects of FTIs on NSCLC cells. Our results suggest that Rheb is a critical target for FTIs therapy in NSCLC.
Authors:
Hang Zheng; Anling Liu; Bin Liu; Minghui Li; Hailang Yu; Xiaojun Luo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  297     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-10-04     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  117-25     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
The Oncology Center of Nanfang Hospital, Southern Medical University, Guangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Carcinoma, Non-Small-Cell Lung / enzymology*,  genetics,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase / antagonists & inhibitors*,  genetics,  metabolism
Humans
Lung Neoplasms / enzymology*,  genetics,  pathology
Monomeric GTP-Binding Proteins / genetics,  metabolism*
Mutation
Neuropeptides / genetics,  metabolism*
Phosphorylation
Piperidines / pharmacology
Prenylation
Proteins
Pyridines / pharmacology
Quinolones / pharmacology
RNA Interference
RNA, Messenger / metabolism
Ribosomal Protein S6 / metabolism
Signal Transduction / drug effects
Transcription Factors / metabolism
Transfection
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Neuropeptides; 0/Piperidines; 0/Proteins; 0/Pyridines; 0/Quinolones; 0/RHEB protein, human; 0/RNA, Messenger; 0/Ribosomal Protein S6; 0/Transcription Factors; 0/mechanistic target of rapamycin complex 1; 15663-27-1/Cisplatin; 192185-72-1/tipifarnib; 193275-84-2/lonafarnib; EC 2.5.1.29/Farnesyltranstransferase; EC 3.6.5.2/Monomeric GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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