Synergistic induction of the Fas (CD95) ligand promoter by Max and NFκB in human non-small lung cancer cells

Zoltan Wiener, Edgar C. Ontsouka, Sabine Jakob, Ralph Torgler, Andras Falus, Christoph Mueller, Thomas Brunner

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fas (CD95/APO-1) ligand is a member of the Tumor Necrosis Factor family and a potent inducer of apoptosis. Fas ligand is expressed in activated T cells and represents a major cytotoxic effector mechanism by which T cells kill their target cells. Activation-induced Fas ligand expression in T cells is under the stringent control of various transcription factors, including nuclear factor κB (NFκB) and c-Myc/Max. There is accumulating evidence that Fas ligand is also expressed by various non-hematopoietic tumor cells, however, little is known about Fas ligand regulation in tumor cells. In this study, we have analyzed the regulation of the Fas ligand gene promoter induction in two non-small cell lung cancer cell lines, with a major focus on the role of the c-Myc/Max transcription factor. Our results revealed that inhibition of c-Myc/Max did not substantially reduce basal levels of Fas ligand promoter activity, nor did overexpression of c-Myc significantly induce promoter activity. In contrast, we observed that overexpression of Max resulted in a marked increase in basal promoter activity and synergistically enhanced phorbolester- and doxorubicin-induced NFκB-mediated Fas ligand promoter activity. These results were confirmed by analyzing endogenous Fas ligand transcription. We conclude that high levels of Max and stress-induced NFκB activation may result in elevated expression of Fas ligand in human lung cancer cells and possibly contribute to Fas ligand-associated immune escape mechanisms.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalExperimental Cell Research
Volume299
Issue number1
DOIs
Publication statusPublished - Sep 10 2004

Keywords

  • Apoptosis
  • Signaling
  • Transcription
  • Tumor cells
  • Tumor necrosis factor family

ASJC Scopus subject areas

  • Cell Biology

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