| Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells. | |
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MedLine Citation:
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PMID: 20554106 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hang Zheng; Anling Liu; Bin Liu; Minghui Li; Hailang Yu; Xiaojun Luo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer letters Volume: 297 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-06 Completed Date: 2010-10-04 Revised Date: 2010-12-13 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 117-25 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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The Oncology Center of Nanfang Hospital, Southern Medical University, Guangzhou, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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 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:
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0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Neuropeptides; 0/Piperidines; 0/Pyridines; 0/Quinolones; 0/RHEB protein, human; 0/RNA, Messenger; 0/Ribosomal Protein S6; 0/Transcription Factors; 0/mTORC1 complex, human; 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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