Brazilian Journal of Medical and Biological Research | |
Collateral methotrexate resistance in cisplatin-selected murine leukemia cells | |
A. Bhushan1  M.p. Hacker2  T.r. Tritton2  | |
[1] ,Idaho State UniversityPocatello ID ,USA | |
关键词: methotrexate transport; resistance; cisplatin; leukemia; phosphorylation; | |
DOI : 10.1590/S0100-879X1999000700005 | |
来源: SciELO | |
【 摘 要 】
Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66) in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.
【 授权许可】
CC BY
All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License
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