A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells.
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منابع مشابه
A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier.
Whereas the major folate transporter, the reduced folate carrier (RFC), has a physiological pH optimum, transport activities for folates and antifolates have been detected with low pH optima. Because the interstitial pH in solid tumors is generally acidic, the mechanisms by which antifolates are transported at low pH could be an important determinant of drug activity under these conditions. The...
متن کاملSensitivity to 5,10-dideazatetrahydrofolate is fully conserved in a murine leukemia cell line highly resistant to methotrexate due to impaired transport mediated by the reduced folate carrier.
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 کاملAnalysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells.
BACKGROUND To evaluate the impact of dihydrofolate reductase (DHFR) and reduced folate carrier (RFC) genes on methotrexate (MTX) resistance in osteosarcoma cells in relation to retinoblastoma (RB1) gene status. MATERIALS AND METHODS A series of human osteosarcoma cell lines-either sensitive or resistant to MTX-and 16 osteosarcoma tumour samples were used in this study. RESULTS In U-2OS MTX-...
متن کاملEffect of arsenic on neural tube in mouse embryo and relation to reduced folate carrier (RFC-1)
Arsenic is an important environmental toxicant which is usually found in drinking water in inorganic form. The hypothesis tested in this investigation is; arsenic exposure causes neural tube defects (NTDs) andthese defects of the central nervous system are more likely related to folate deficiency during fetal life. In this study, sodium arsenate was administered via intraperitoneal route at a r...
متن کاملInfluence of reduced folate carrier and dihydrofolate reductase genes on methotrexate-induced cytotoxicity.
PURPOSE The aim of this study is to investigate the effect of genetic variations and the expression of the reduced folate carrier (RFC) and dihydrofolate reductase (DHFR) on the drug sensitivity to methotrexate (MTX) in different cancer cell lines. MATERIALS AND METHODS We examined the six human cancer cell lines (MCF-7, AGS, A549, NCI-H23, HCT-116 and Saos-2). The cytotoxicity of MTX was mea...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1994
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(17)42301-5