Selection for methotrexate resistance in mammalian cells bearing a Drosophila dihydrofolate reductase transgene: Methotrexate resistance in transgenic mammalian cells.
作者： Joslynn G. Affleck , Shaun M. Nowickyj , Virginia K. Walker
DOI: 10.1007/S10565-009-9122-1
关键词:
摘要: Antifolates, such as methotrexate (MTX), are the treatment of choice for numerous cancers. MTX inhibits dihydrofolate reductase (DHFR), which is essential cell growth and proliferation. Mammalian cells can acquire resistance to antifolate through a variety mechanisms but decreased titers due changes in drug efflux or influx, alternatively, amplification DHFR gene most commonly acquired mechanisms. In Drosophila, however, resistant phenotype has only been observed occur by mutation resulting MTX-resistant DHFR. It unclear if differences structure and/or genome organization between Drosophila mammals contribute resistance. To investigate involved, Dhfr cDNA was transfected into line CHO that do not express endogenous These transgenic cells, together with wild-type were selected 19 months increasing concentrations MTX, from 50- 200-fold over initial concentration. Since appears have amplified several fold mammalian difference may mechanism
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