Antifolate Resistance in a HeLa Cell Line Associated With Impaired Transport Independent of the Reduced Folate Carrier
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Impaired CREB-1 phosphorylation in antifolate-resistant cell lines with down-regulation of the reduced folate carrier gene.
The human reduced folate carrier (hRFC) is the dominant transporter for the uptake of antifolates used in cancer chemotherapy. We have shown recently that decreased cAMP-responsive element (CRE)-dependent transcription contributes to the loss of hRFC gene expression in multiple antifolate-resistant cell lines. This was associated with markedly decreased levels of phosphorylated cAMP response el...
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5-Aminoimidazole-4-carboxamide riboside (AICAR), an agent with diverse pharmacological properties, augments transport of folates and antifolates. This report further characterizes this phenomenon and defines the mechanism by which it occurs. Exposure of HeLa cells to AICAR resulted in augmentation of methotrexate, 5-formyltetrahydrofolate, and 5-methyltetrahydrofolate initial rates and net upta...
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A murine leukemia cell line was identified that is highly resistant to methotrexate (MTX), due to impaired transport, but fully sensitive to 5,10-dideazatetrahydrofolate (DDATHF). A valine-to-methionine substitution at amino acid 104 in the reduced folate carrier (RFC1) explains this disparity in drug resistance. Transfection of the V104M cDNA into an RFC1-deficient cell line markedly increased...
متن کاملThe reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women.
Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk v...
متن کاملFolate receptor and human reduced folate carrier expression in HepG2 cell line exposed to fumonisin B1 and folate deficiency.
Fumonisin B1 (FB1) induces apoptosis and decreases the cellular uptake of 5-methyltetrahydrofolate. Two folate transporters (folate receptor, FR, and Reduced Folate Carrier, hRFC1) are involved in the cell uptake of folate. We aimed to study whether FB1 modifies the expression of the FR and the hRFC1 and whether its apoptotic effect is influenced by folate. Incubation of HepG2 cells with FB1 in...
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ژورنال
عنوان ژورنال: Clinical Cancer Research
سال: 2004
ISSN: 1078-0432,1557-3265
DOI: 10.1158/1078-0432.ccr-04-0932