Document Detail


The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS.
MedLine Citation:
PMID:  10477917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI-277 (20 microM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radiosensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G(2)/M-phase arrest in both cell types. These results clearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G(2)/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radiosensitizers of certain human tumors with wild-type RAS.
Authors:
E Cohen-Jonathan; C Toulas; I Ader; S Monteil; C Allal; J Bonnet; A D Hamilton; S M Sebti; N Daly-Schveitzer; G Favre
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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:  Radiation research     Volume:  152     ISSN:  0033-7587     ISO Abbreviation:  Radiat. Res.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-20     Completed Date:  1999-10-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  404-11     Citation Subset:  IM; S    
Affiliation:
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA/UPRES 2048, Faculté des Sciences Pharmaceutiques, Université Paul Sabatier, Centre de Lutte Contre le Cancer Claudius Regaud, 20-24 rue du Pont St-Pierre, 31052 Toulouse Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Alkyl and Aryl Transferases / antagonists & inhibitors*
Cell Survival / drug effects,  radiation effects
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase
Fibroblast Growth Factor 2 / antagonists & inhibitors*
Hela Cells
Humans
Methionine / analogs & derivatives*,  pharmacology
Radiation Tolerance / drug effects*
Grant Support
ID/Acronym/Agency:
CA-76661/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/FTI 277; 103107-01-3/Fibroblast Growth Factor 2; 63-68-3/Methionine; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.29/Farnesyltranstransferase

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