Involvement of gene polymorphisms of the folate pathway enzymes in gene expression and anticancer drug sensitivity using the NCI-60 panel as a model.
Folate, a vitamin of the B group involved in one-carbon group metabolism, plays an important role in DNA synthesis and methylation. Several polymorphisms in the genes involved in folate uptake and biotransformations have been shown to be associated to the risk of cancer and to anticancer drug respon...
| Publicado en: | European Journal of Cancer Vol. 45; no. 13; pp. 2391 - 2402 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Pergamon Press - An Imprint of Elsevier Science
Sep2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105444365&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105444365 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09598049 1VW jtl: European Journal of Cancer issn: 09598049 maglogo: N pubinfo: dt: Sep2009 vid: 45 iid: 13 pid: 2410 pub: Pergamon Press - An Imprint of Elsevier Science artinfo: ui: 105444365 2010420305 10.1016/j.ejca.2009.05.013 NLM19501504 105444365 ppf: 2391 ppct: 11 formats: tig: atl: Involvement of gene polymorphisms of the folate pathway enzymes in gene expression and anticancer drug sensitivity using the NCI-60 panel as a model. aug: au: Charasson V Hillaire-Buys D Solassol I Laurand-Quancard A Pinguet F Le Morvan V Robert J affil: Laboratoire de Pharmacologie et Toxicologie Clinique, Hôpital Lapeyronie et Université de Montpellier 1, 34295 Montpellier, France. sug: subj: Antineoplastic Agents Therapeutic Use Drug Resistance, Neoplasm Genes Neoplasms Oxidoreductases Polymorphism, Genetic Cells Genetic Markers Neoplasms Drug Therapy Transferases ab: Folate, a vitamin of the B group involved in one-carbon group metabolism, plays an important role in DNA synthesis and methylation. Several polymorphisms in the genes involved in folate uptake and biotransformations have been shown to be associated to the risk of cancer and to anticancer drug response. We studied common polymorphisms in MTHFR (N(5,10)-methylene-tetrahydrofolate reductase), MTHFD1 (N(5,10)-methylene-tetrahydrofolate dehydrogenase), MTR (methionine synthetase) and SLC19A1 (reduced folate carrier) in the panel of 60 human tumour cell lines established by the NCI for anticancer drug screening and we tentatively associated these polymorphisms with gene expression and drug cytotoxicity as extracted from the public database of the Developmental Therapeutic Programme. We observed a consistent and highly significant association between the presence of the variant C allele of the A>C1298 polymorphism of MTHFR and the sensitivity to many anticancer drugs belonging to the classes of antifolates, antimetabolites, alkylating agents and, to a lesser extent, topoisomerase inhibitors. In contrast, the T variant allele of the C>T677 variation of MTHFR was rather associated to lower sensitivity of the cell lines towards anticancer drugs (alkylating agents, antifolates and antimetabolites) but with much lower effects than the A>C1298 variation. The polymorphisms of the other genes studied were not associated with differences in anticancer drug sensitivity, but the expression of the SLC19A1 gene was significantly correlated with the sensitivity to several drugs (antifolates, thiopurines, nitrosoureas, and DACH-platinum drugs). We concluded that the NCI-60 panel may constitute a good starting point for implementing clinical studies aimed at discovering and validating predictive genetic markers of drug efficacy and/or toxicity. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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