Correlation of altered tyrosine phosphorylation with methotrexate resistance in a cisplatin-resistant subline of L1210 cells

Collateral resistance to cisplatin and methotrexate has been reported in several cell lines. A murine leukemia cell line (L1210/DDP) selected for cisplatin resistance also has been shown to be highly resistant to methotrexate. Of the mechanisms proposed for methotrexate resistance, only changes in m...

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Bibliographic Details
Published in:Biochemical pharmacology 1996-02, Vol.51 (4), p.477-482
Main Authors: Bhushan, Alok, Wroblewski, Diana, Xuan, Yongzhi, Tritton, Thomas R., Hacker, Miles P.
Format: Article
Language:English
Subjects:
Affinity Labels
Animals
Antineoplastic agents
Biological and medical sciences
Biological Transport, Active
Blotting, Western
Chemotherapy
cisplatin
Cisplatin - toxicity
Clone Cells
drug resistance
Drug Resistance, Neoplasm
drug transport
Electrophoresis, Polyacrylamide Gel
L1210 cells
Leukemia L1210 - metabolism
Medical sciences
Membrane Proteins - isolation & purification
Membrane Proteins - metabolism
methotrexate
Methotrexate - metabolism
Methotrexate - toxicity
Mice
Molecular Weight
Pharmacology. Drug treatments
Phosphoproteins - isolation & purification
Phosphoproteins - metabolism
Phosphotyrosine - metabolism
Tumor Cells, Cultured
tyrosine phosphorylation
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Summary:Collateral resistance to cisplatin and methotrexate has been reported in several cell lines. A murine leukemia cell line (L1210/DDP) selected for cisplatin resistance also has been shown to be highly resistant to methotrexate. Of the mechanisms proposed for methotrexate resistance, only changes in methotrexate transport into the cells were found in an earlier report. Methotrexate enters mammalian cells via an active transport system. In the present study, we demonstrated that the transport into the cell may be impaired in the resistant cells due to altered tyrosine phosphorylation of a membrane protein with a molecular mass of 66 kDa. This alteration was manifested by altered tyrosine phosphorylation of the 66 kDa protein and may be an underlying modification that renders the cells resistant to methotrexate. These results suggest involvement of tyrosine phosphorylation in folate transport and methotrexate resistance in L1210/DDP cells.
ISSN:0006-2952
1873-2968
DOI:10.1016/0006-2952(96)84208-0