PMID: 8598463Jan 1, 1996Paper

Susceptibility to TNF in the presence of inhibitors of transcription or translation is dependent on the activity of cytosolic phospholipase A2 in human melanoma tumor cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
C Voelkel-JohnsonS M Laster

Abstract

In this study, we have examined the relationship between the expression of the high molecular weight, cytosolic form of PLA2 (cPLA2) and ability of inhibitors of transcription or translation (ITT) to induce susceptibility to TNF. S Susceptibility to lysis was assayed by 51CR release, and the expression of cPLA2 was assayed by activity assay and by Western blot. The panel of cells that we examined included two murine cell lines, six human melanoma-derived cell lines, two samples of freshly explanted melanoma tumor tissue, and a culture of normal epidermal melanocytes. Our experiments revealed a near perfect correlation between the activity of cPLA2 per cell and susceptibility to TNF in the presence of either cycloheximide (CHI) or actinomycin D (r = 0.97). These results suggest that the activity of cPLA2 is both necessary and rate-limiting in this form of programmed cell death, conclusions that were confirmed in transfection experiments and in experiments with antisense oligonucleotides. Over-expression of cPLA2 in two melanoma-derived cell lines, WM793 and SK-MEL-131, led to enhanced susceptibility to TNF and CHI. Conversely, suppression of cPLA2 with antisense oligonucleotides dramatically decreased susceptibility to TNF and C...Continue Reading

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