EXPRESSION OF 2 50 KDA PROTEINS IS ASSOCIATED WITH SENSITIVITY TOWARDS ETHERLIPID ANALOGS IN THE HUMAN LEUKEMIA-CELL LINE HL-60

Hexadecylphosphocholine (HePC) is a new etherphospholipid derived subs tance with pronounced antineoplastic activity. So far the mode of acti on of this compound has not been resolved. Therefore, we decided to ap proach this problem by generating HePC resistant sublines of susceptib le cells. The human leukaemia cell Line HL 60 was successfully adapted to high concentrations of HePC over a period of 14 months. The resist ant cell line HL 60 R shows similar functional characteristics as the original HL 60. Both lines can be induced to terminal differentiation into a granulocytic phenotype by DMSO. In this process, normal HL 60 c ells also become resistant towards HePC. Determinations of cellular me mbrane Lipid composition did not show significant changes, which would explain the resistance mechanism. Analysis of cellular proteins by 2D -gelelectrophoresis revealed two 50 kDa proteins expressed in HL 60 an d differentiated HL 60 cells, which were not expressed in HL 60 R. Rev ersion of resistance of HL 60 R after prolonged cultivation without He PC led to re-expression of the two proteins, indicating at a possible involvement of these proteins in HePC sensitivity. (C) 1997 Elsevier S cience Ltd.