THE ETHER LIPID 1-OCTADECYL-2-METHYL-RAC-GLYCERO-3-PHOSPHOCHOLINE INDUCES EXPRESSION OF FOS AND JUN PROTOONCOGENES AND ACTIVATES AP-1 TRANSCRIPTION FACTOR IN HUMAN LEUKEMIC-CELLS

The ether lipid analogue 1-octadecyl-2-methyl-rac-glycero-3-phosphocho line (ET-18-OCH3) has been recently shown to induce apoptosis in the h uman leukaemic HL-60 and U937 myeloid cell lines [Mollinedo, Martinez- Dalmau and Modolell (1993) Biochem. Biophys. Res. Commun. 192, 603-609 ]. We have found that ET-18-OCH3 is also able to promote apoptosis in the human leukaemic Jurkat T lymphoid cell line. This lymphoid cell li ne as well as the two myeloid HL-60 and U937 cell lines incorporated s ignificant amounts of exogenously added radiolabelled ET-18-OCH,. Addi tion of ET-18-OCH3 to these human leukaemic cells induced an increase in the steady-state mRNA levels of fos and jun proto-oncogenes, compon ents of the transcription factor AP-1. These increases in fos and jun mRNA levels were associated with the activation of the AP-1 transcript ion factor after addition of ET-18-OCH3 to human leukaemic cells, as a ssessed by an enhanced binding activity of transcription factor AP-1 t o its cognate DNA sequence as well as by stimulation of transcription from an AP-1 enhancer element. These data demonstrate that the ether l ipid ET-18-OCH3 can affect gene expression by inducing expression of f os and jun proto-oncogenes and by modulating the activity of transcrip tion factor AP-1.