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Expression of TRAIL (Apo2L), DR4 (TRAIL receptor 1), DR5 (TRAIL receptor 2) and TRID (TRAIL receptor 3) genes in multidrug resistant human acute myeloid leukemia cell lines that overexpress MDR 1 (HL60/Tax) or MRP (HL60/AR).

Abstract
Previously we have reported a differential expression of CD95/CD95L and Bcl-2 family of genes in multidrug resistant tumor cells. TRAIL, a member of the TNF receptor family, induces apoptosis in many tumor cells by binding to DR4 (TRAIL receptor 1) and DR5 (TRAIL receptor 2). In contrast, TRAIL-induced apoptosis is prevented by a decoy receptor (DcR1, TRID or TRAIL receptor 3). In the present study, we compared the expression of TRAIL, DR4, DR5, and TRID between a drug sensitive HL60, a myeloid leukemia cell line, and its multidrug resistant (MDR) sublines that either overexpressed MDR 1 gene (HL60/Tax) or MRP gene (HL60/AR), using RT-PCR. TRAIL mRNA was expressed in HL60 cells but was present in low levels in HL60/AR cells and was completely lacking in HL60/Tax cells. Both DR4 and DR5 were undetectable in HL60/Tax but were present at comparable levels in HL60/AR and drug sensitive HL60 cells. TRID were absent in HL60 and HL60/Tax cells, but was present in low but comparable levels in peripheral blood mononuclear cells and HL60/AR cells. These data suggest that the multidrug resistance in MDR HL60 cell lines, regardless of overexpression of MDR 1 or MRP, may be due to different mechanisms. In HL60/AR cells it appears that MDR may be due to decreased expression of TRAIL and constitutive expression of TRID, whereas in HL60/Tax cells, MDR could be due to the absence of TRAIL and/or DR4 and DR5.
AuthorsC H Kim, S Gupta
JournalInternational journal of oncology (Int J Oncol) Vol. 16 Issue 6 Pg. 1137-9 (Jun 2000) ISSN: 1019-6439 [Print] Greece
PMID10811986 (Publication Type: Journal Article)
Chemical References
  • ATP-Binding Cassette Transporters
  • Apoptosis Regulatory Proteins
  • Fungal Proteins
  • GPI-Linked Proteins
  • MDR1 protein, Filobasidiella neoformans
  • Membrane Glycoproteins
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 10c
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFRSF10C protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
Topics
  • ATP-Binding Cassette Transporters (metabolism)
  • Apoptosis Regulatory Proteins
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Fungal Proteins
  • GPI-Linked Proteins
  • HL-60 Cells (metabolism)
  • Humans
  • Membrane Glycoproteins (metabolism)
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins (metabolism)
  • RNA, Messenger (metabolism)
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor (metabolism)
  • Receptors, Tumor Necrosis Factor, Member 10c
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha (metabolism)

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