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

Biochem J. 1994 Sep 1;302 ( Pt 2)(Pt 2):325-9. doi: 10.1042/bj3020325.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Base Sequence
  • Blotting, Northern
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, fos*
  • Genes, jun*
  • Humans
  • Leukemia / genetics*
  • Molecular Sequence Data
  • Phospholipid Ethers / pharmacology*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured

Substances

  • 3-octadecyl-2-methylglycero-1-phosphocholine
  • Phospholipid Ethers
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger