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

Biochem Biophys Res Commun. 2000 Sep 24;276(2):466-71. doi: 10.1006/bbrc.2000.3512.

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 ( approximately 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-gamma (IFN-gamma)-mediated induction. Furthermore, induction of TRAIL mRNA levels was demonstrated in HT29 and Caco-2 cells with IFN-gamma treatment suggesting an important role for this cytokine in TRAIL expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Caco-2 Cells
  • Cloning, Molecular
  • DNA / analysis
  • Gene Expression Regulation*
  • Genome, Human
  • HT29 Cells
  • Humans
  • Interferon-gamma / physiology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / isolation & purification
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Sequence Analysis, DNA
  • TNF-Related Apoptosis-Inducing Ligand
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / isolation & purification

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • DNA

Associated data

  • GENBANK/AF178756