| The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS. | |
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MedLine Citation:
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PMID: 10477917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Radiation research Volume: 152 ISSN: 0033-7587 ISO Abbreviation: Radiat. Res. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-10-20 Completed Date: 1999-10-20 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0401245 Medline TA: Radiat Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 404-11 Citation Subset: IM; S |
Affiliation:
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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. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkyl and Aryl Transferases
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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:
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CA-76661/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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