The TRAIL-receptor-1: TRAIL-receptor-3 and-4 ratio is a predictor for TRAIL sensitivity of cancer cells
The TRAIL-receptor-1: TRAIL-receptor-3 and-4 ratio is a predictor for TRAIL sensitivity of cancer cells
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DOI：
10.3892/or_00000353
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发表时间：
2009-05-01
期刊：
影响因子：
4.2
通讯作者：
Zwacka, Ralf Michael
中科院分区：
文献类型：
--
作者：
Bueneker, Chirlei;Mohr, Andrea;Zwacka, Ralf Michael
肿瘤坏死因子相关的凋亡诱导配体(TRAIL)是许多肿瘤细胞中有效的凋亡诱导剂。然而，相当大比例的肿瘤是耐药的，这为未来成功的基于TRAIL的治疗方案设置了一个主要障碍。在这种情况下，能够识别对TRAIL有反应的肿瘤将是一个重大优势。TRAIL受体(TRAIL-R1和TRAIL-R2)和不能传递凋亡信号但具有抑制功能的两种受体(TRAIL-R3和TRAIL-R4)的存在使TRAIL信号转导变得复杂。我们分析了四种膜结合TRAIL受体在不同来源的癌细胞系、原代癌细胞和正常细胞中的表面表达，发现TRAIL敏感性与TRAIL-R1的单独表达有很好的相关性，但当分析TRAIL-R1/TRAIL-R3+TRAIL-R4的比率时，相关性更好。TRAIL-R1单独或与TRAIL-R4联合在PANC-1细胞中过表达的实验结果证实了我们的相关结果。与表面表达-凋亡相关分析相似，我们发现TRAIL敏感性与TRAIL-R1/TRAIL-R3+TRAIL-R4的mRNA水平比值高度相关。价值为
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