The TRAIL-receptor-1: TRAIL-receptor-3 and -4 ratio is a predictor for TRAIL sensitivity of cancer cells

Oncol Rep. 2009 May;21(5):1289-95. doi: 10.3892/or_00000353.


The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in many cancer cells. However, a significant proportion of tumours are TRAIL-resistant erecting a major hurdle for a successful TRAIL-based treatment regimen in the future. In this context, it would be a major advantage to be able to identify the tumours that respond to TRAIL. The existence of two apoptosis-inducing receptors (TRAIL-R1 and TRAIL-R2) and two receptors that cannot transmit an apoptotic signal and have an inhibitory function (TRAIL-R3 and TRAIL-R4) make TRAIL signalling complicated. We analysed the surface expression of all four membrane-bound TRAIL receptors in cancer cell lines of various origin and primary cancer and normal cells and found a good correlation between TRAIL-sensitivity and the expression of TRAIL-R1 alone, but an even better correlation when a ratio of TRAIL-R1/TRAIL-R3+TRAIL-R4 was analysed. Experimental overexpression of TRAIL-R1 alone or in combination with TRAIL-R4 in PANC-1 cells confirmed our correlation results. Similar to the surface expression-apoptosis correlation analysis we found a high correlation between TRAIL-sensitivity and the mRNA level ratio of TRAIL-R1/TRAIL-R3+TRAIL-R4. A value of <0.85 for the ratio predicted TRAIL resistance in both protein and RNA analysis. Hence, TRAIL receptor RNA expression analysis by real-time PCR might be a feasible approach to predict possible TRAIL-responses in individual tumour samples.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor, Member 10c / biosynthesis
  • Receptors, Tumor Necrosis Factor, Member 10c / genetics
  • Recombinant Proteins / pharmacology
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*


  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFSF10 protein, human