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Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier

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dc.contributor.authorYang, Rui-
dc.contributor.authorLi, Wei-Wei-
dc.contributor.authorHoang, Bang H-
dc.contributor.authorKim, Hansoo-
dc.contributor.authorBanerjee, Debabrata-
dc.contributor.authorKheradpour, Albert-
dc.contributor.authorHealey, John H-
dc.contributor.authorMeyers, Paul A-
dc.contributor.authorBertino, Joseph R-
dc.contributor.authorGorlick, Richard-
dc.date.accessioned2010-04-05T04:08:16Z-
dc.date.available2010-04-05T04:08:16Z-
dc.date.issued2008-05-03-
dc.identifier.citationBMC Cancer 8:124-132en
dc.identifier.issn1471-2407 (Electronic)-
dc.identifier.urihttps://hdl.handle.net/10371/62512-
dc.description.abstractBACKGROUND: Methotrexate (MTX) uptake is mediated by the reduced folate carrier (RFC). Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied. METHODS: In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8), including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines. RESULTS: A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, p < 0.05) was identified between the promoter methylation and RFC mRNA levels in this a panel of malignant cell lines. CONCLUSION: This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.subjectAntineoplastic Agents/administration & dosageen
dc.subjectBreast Neoplasms/drug therapy/enzymology/genetics/pathologyen
dc.subjectCell Line, Tumoren
dc.subject*DNA Methylationen
dc.subjectDown-Regulationen
dc.subjectDrug Resistance, Neoplasm/drug effectsen
dc.subjectDrug Therapyen
dc.subjectFemaleen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHumansen
dc.subjectMembrane Transport Proteins/*biosynthesis/*geneticsen
dc.subjectMethotrexate/administration & dosageen
dc.subjectOsteosarcoma/drug therapy/enzymology/genetics/pathologyen
dc.subject*Promoter Regions, Geneticen
dc.subjectRNA, Messenger/biosynthesis/*geneticsen
dc.titleQuantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrieren
dc.typeArticleen
dc.contributor.AlternativeAuthor김한수-
dc.identifier.doi10.1186/1471-2407-8-124-
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