Kim C H, Gupta S
Molecular Biology Laboratory, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Int J Oncol. 2000 Jun;16(6):1137-9. doi: 10.3892/ijo.16.6.1137.
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.
此前我们报道过，在多药耐药肿瘤细胞中CD95/CD95L和Bcl-2基因家族存在差异表达。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是肿瘤坏死因子受体家族的成员，通过与死亡受体4（DR4，TRAIL受体1）和死亡受体5（DR5，TRAIL受体2）结合，诱导许多肿瘤细胞凋亡。相比之下，诱骗受体（DcR1、TRID或TRAIL受体3）可阻止TRAIL诱导的细胞凋亡。在本研究中，我们采用逆转录聚合酶链反应（RT-PCR），比较了药物敏感的髓系白血病细胞系HL60及其多药耐药（MDR）亚系（分别过表达MDR 1基因的HL60/Tax和过表达多药耐药相关蛋白基因的HL60/AR）中TRAIL、DR4、DR5和TRID的表达情况。TRAIL信使核糖核酸（mRNA）在HL60细胞中表达，但在HL60/AR细胞中表达水平较低，在HL60/Tax细胞中则完全缺失。在HL60/Tax细胞中未检测到DR4和DR5，但在HL60/AR细胞和药物敏感的HL60细胞中，二者表达水平相当。TRID在HL60和HL60/Tax细胞中不存在，但在外周血单个核细胞和HL60/AR细胞中表达水平较低但相当。这些数据表明，MDR HL60细胞系中的多药耐药，无论MDR 1或多药耐药相关蛋白是否过表达，可能是由于不同机制所致。在HL60/AR细胞中，多药耐药可能是由于TRAIL表达降低和TRID的组成性表达，而在HL60/Tax细胞中，多药耐药可能是由于TRAIL和/或DR4及DR5的缺失。
