The ether lipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine induces expression of fos and jun proto-oncogenes and activates AP-1 transcription factor in human leukaemic cells.
The ether lipid analogue 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) has been recently shown to induce apoptosis in the human 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 line as well as the two myeloid HL-60 and U937 cell lines incorporated significant amounts of exogenously added radiolabelled ET-18-OCH3. Addition of ET-18-OCH3 to these human leukaemic cells induced an increase in the steady-state mRNA levels of fos and jun proto-oncogenes, components of the transcription factor AP-1. These increases in fos and jun mRNA levels were associated with the activation of the AP-1 transcription factor after addition of ET-18-OCH3 to human leukaemic cells, as assessed by an enhanced binding activity of transcription factor AP-1 to its cognate DNA sequence as well as by stimulation of transcription from an AP-1 enhancer element. These data demonstrate that the ether lipid ET-18-OCH3 can affect gene expression by inducing expression of fos and jun proto-oncogenes and by modulating the activity of transcription factor AP-1.
Mollinedo
F
F
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Gajate
C
C
Modolell
M
M
D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015152:Blotting, Northern; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D010742:Phospholipid Ethers / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
C076164:3-octadecyl-2-methylglycero-1-phosphocholine; D010742:Phospholipid Ethers; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger