A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells
作者： K.H. Dixon , B.C. Lanpher , J. Chiu , K. Kelley , K.H. Cowan
DOI: 10.1016/S0021-9258(17)42301-5
关键词:
摘要: Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes isolation expression of cDNA clone that restores RFC activity to human breast cancer defective in this transporter. The codes for peptide (mRFC1) 58 kDa, whose hydropathy plot, resembling those mammalian sugar transporters, predicts it may be member superfamily transporter genes. Transfection methotrexate-resistant (MTXR) ZR-75-1 with an vector, pRFC1, their ability methotrexate. Furthermore, transport methotrexate into pRFC1-transfected is blocked by 10-fold molar excess folate, 5-formyltetrahydrofolic acid, but unaffected folic acid. increase uptake observed MTXR reverses resistance antitumor agent.
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