FUNCTIONAL EXPRESSION OF THE HUMAN MDR1 GENE IN ESCHERICHIA-COLI

In this preliminary study, we report the cloning of the human MDR1 cDN A into a prokaryotic expression vector and the consequent functional e xpression of heterologous P-glycoprotein in Escherichia coli. We demon strate increased resistance to the P-glycoprotein substrates TPA(+), T PP+, and puromycin; reduced accumulation of TPP+ and tetracycline by r esistant 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 prokaryoti c ABC trans porters and other efflux transporters argues for a more co mplete study of the consequences pertaining to the expression of human P-glycoprotein in E. coli. (C) 1996 Academic Press, Inc.