| First Author | Dixon KH | Year | 1994 |
| Journal | J Biol Chem | Volume | 269 |
| Issue | 1 | Pages | 17-20 |
| PubMed ID | 8276792 | Mgi Jnum | J:16454 |
| Mgi Id | MGI:64534 | Doi | 10.1016/s0021-9258(17)42301-5 |
| Citation | Dixon KH, et al. (1994) A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells. J Biol Chem 269(1):17-20 |
| abstractText | Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this antitumor agent. |
