THE GENE ENCODING VACUOLAR H+-ATPASE SUBUNIT C IS OVEREXPRESSED IN MULTIDRUG-RESISTANT HL-60 CELLS

Previous studies have suggested that vacuolar H+-ATPase activity may play a role in modulating drug transport mechanisms in multidrug resistant HL60 cells. In the present study we have used a cDNA of human vacuolar H+-ATPase subunit C (SC-H+-ATPase) to analyze expression of this gene in HL70 cells isolated for resistance to adriamycin or vincristine. The results demonstrate that development of resistance to either agent results in a major increase in the levels of SC-H+-ATPase mRNA. Furthermore in resistant cells which have partially reverted to drug sensitivity there is a parallel reduction in SC-H+-ATPase mRNA levels. Southern blot analysis shows that the SC-H+-ATPase gene is not amplified in the resistant cells. These results therefore demonstrate a correlation between the development of multidrug resistance and enhanced expression of the SC-H+-ATPase gene. © 1992.