Functional expression of the human MDR1 gene in Escherichia coli

In this preliminary study, we report the cloning of the human MDR1 cDNA into a prokaryotic expression vector and the consequent functional expression of heterologous P-glycoprotein in Escherichia coli. We demonstrate increased resistance to the P-glycoprotein substrates TPA(+), TPP+, and puromycin; reduced accumulation of TPP+ and tetracycline by resistant cells; and the expression of a full-length immunoreac tive P-glycoprotein molecule in the membrane fraction of resistant cells. The obvious structural and func tional similarities of P-gp to prokaryotic ABC trans porters and other efflux transporters argues for a more complete study of the consequences pertaining to the expression of human P-glycoprotein in E. coli. (C) 1996 Academic Press, Inc.