Ryu H. S., Chang K. H., Chang S. J., Kim M. S., Joo H. J., Oh K. S.
Departments of Obstetrics and Gynecology and Pathology, Ajou University School of Medicine, Suwon, Korea.
Int J Gynecol Cancer. 2000 Sep;10(5):417-424. doi: 10.1046/j.1525-1438.2000.010005417.x.
Apoptosis is an intrinsic and fundamental biologic process that plays a critical role in the normal development of multicellular organisms and in the maintainance of tissue homeostasis. Some of the well known regulators of apoptosis are cytokines of the tumor necrosis factor (TNF) ligand family, such as Fas ligand (Fas L) and TNF, which induce apoptosis by activation of their corresponding receptors, Fas and TNFR-1. Recently, a new member of the TNF family known as TRAIL (TNF-related apoptosis-inducing ligand) was identified and shown to induce p53-independent apoptosis in a variety of tumor cell lines but not in normal cells. Four human receptors for TRAIL were also recently identified and designated TRAIL-R1, -R2, -R3, and -R4. The aim of this study is to examine whether TRAIL and TRAIL receptors (-R1, -R2, -R3) are expressed in uterine cervical cancer and whether it is correlated with apoptosis, TRAIL, and TRAIL receptors. The subjects were 20 patients who were diagnosed with cervical cancer. Western blotting was performed in nine cases and immunohistochemical staining for TRAIL and TRAIL receptors (-R1, -R2, -R3) and TUNEL method for detection of apoptosis was performed in 11 cases. There were proteins for TRAIL, TRAIL-R1, -R2, and -R3 in tissues from cervical cancer. All TRAIL receptors were expressed in both normal cervical epithelium and tumor cells, and TRAIL-R1 and -R2 were more strongly expressed in tumor cells than normal epithelium (P < 0.05). Apoptosis correlated with expression of TRAIL-R1 and -R2 (P < 0.05). This study suggests that TRAIL induces apoptosis in cervical cancer through its receptors.
细胞凋亡是一种内在的基本生物学过程，在多细胞生物体的正常发育以及组织稳态的维持中发挥着关键作用。一些广为人知的细胞凋亡调节因子是肿瘤坏死因子（TNF）配体家族的细胞因子，如Fas配体（Fas L）和TNF，它们通过激活相应受体Fas和TNFR-1来诱导细胞凋亡。最近，一种名为TRAIL（TNF相关凋亡诱导配体）的TNF家族新成员被鉴定出来，并显示在多种肿瘤细胞系中可诱导不依赖p53的细胞凋亡，但在正常细胞中则不会。最近还鉴定出了四种人类TRAIL受体，并将其命名为TRAIL-R1、-R2、-R3和-R4。本研究的目的是检测TRAIL及其受体（-R1、-R2、-R3）在子宫颈癌中是否表达，以及它是否与细胞凋亡、TRAIL和TRAIL受体相关。研究对象为20例被诊断为宫颈癌的患者。对9例进行了蛋白质印迹分析，对11例进行了TRAIL及其受体（-R1、-R2、-R3）的免疫组织化学染色以及用于检测细胞凋亡的TUNEL法。宫颈癌组织中有TRAIL、TRAIL-R1、-R2和-R3的蛋白质。所有TRAIL受体在正常宫颈上皮和肿瘤细胞中均有表达，且TRAIL-R1和-R2在肿瘤细胞中的表达比正常上皮更强（P < 0.05）。细胞凋亡与TRAIL-R1和-R2的表达相关（P < 0.05）。本研究表明，TRAIL通过其受体在宫颈癌中诱导细胞凋亡。
