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Up-Regulated Transport of Methotrexate and 5-Methyltetrahydrofolate in a Human Breast Cancer Cell Line

  • Frederika Mandelbaum-Shavit
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 338)

Abstract

In a majority of tumor cells, a high affinity/low capacity transport system mediates the uptake of 5-substituted reduced folates and the analog methotrexate (MTX),1–3 an important chemotherapeutic agent. The relatively low levels of the MTX carrier prompted studies on selecting variants able to up-regulate this system. Such strategy was first introduced by Sirotriak4, who by cultivating L1210 cells in progressively decreasing and growth limiting concentrations of (6R,S)-5-formyltetrahydrofolate (5-HCO-H4PteGlu), selected cells with increased transport capacities for this compound. A similar approach was used to obtain a variant of human erythroleukemia line that exhibited elevated influx.Vmax for MTX and 5-HCO-H4PteGlu relative to the parental cells5. Up-regulation of the reduced folate carrier was also found in human CCRF-CEM leukemia cells adapted to grow on < 1 nM 5-HCO-H4PteGIu,t6 whereas cultivation in the presence of low concentrations of folate induced an increased level of a membrane-associated folate-binding protein7,8.

Keywords

Human Breast Cancer Cell Line Reduce Folate Carrier Transport Buffer Dialyze Fetal Bovine Serum Human Erythroleukemia Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Frederika Mandelbaum-Shavit
    • 1
  1. 1.Department of BacteriologyHebrew University-Hadassah Medical SchoolJerusalemIsrael

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