Isolation and molecular characterization of the 5'-upstream region of the human TRAIL gene

Qingding Wang, Yanshan Ji, Xiaofu Wang, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

TRAIL, a novel member of the TNF family, acts through membrane receptors to induce apoptosis of activated T lymphocytes and may represent a mechanism for the 'immune escape' of certain cancers. Various cytokines appear to increase expression of other TNF family members; however, the regulation of TRAIL has not been defined. The purpose of this study was to assess molecular mechanisms regulating TRAIL gene expression in human colon cancers. In this study, we have cloned the human TRAIL (hTRAIL) promoter (~1.6 kb) and identified a number of putative transcription factor binding sites such as NFAT, AP-1 and Sp1 sequences which are important for the expression of other TNF family members. Transient transfections of 5'-deletion promoter constructs into either Caco-2 or HT29 colon cancer cells identified TRAIL promoter regions critical for both basal and interferon-γ (IFN-γ)-mediated induction. Furthermore, induction of TRAIL mRNA levels was demonstrated in HT29 and Caco-2 cells with IFN-γ treatment suggesting an important role for this cytokine in TRAIL expression. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)466-471
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume276
Issue number2
DOIs
StatePublished - Sep 24 2000

Bibliographical note

Funding Information:
The authors thank Eileen Figueroa and Karen Martin for preparation of the manuscript. This work was funded by grants from the National Institutes of Health (R01 DK48498, R01 AG10885, P01 DK35608).

Keywords

  • Caco-2
  • HT29
  • Human colon cancers
  • IFN-γ
  • TNF family
  • TRAIL

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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