Identification of a human glioma antigen, SOX6, recognized by patients' sera
Identification of a human glioma antigen, SOX6, recognized by patients' sera
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DOI：
10.1038/sj.onc.1207252
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发表时间：
2004-02-19
期刊：
影响因子：
8
通讯作者：
Toda, M
中科院分区：
文献类型：
--
作者：
Ueda, R;Iizuka, Y;Toda, M
为筛选胶质瘤的肿瘤抗原，采用重组表达克隆技术，从人睾丸cDNA文库中筛选胶质瘤抗原。在该筛选中，最常分离的抗原是SOX 6，其是一种含有Sry相关高迁移率族（HMG）盒的基因。SOX 6是一种转录因子，在发育中的中枢神经系统和小鼠胚胎软骨形成的早期阶段特异性表达。在36例胶质瘤患者中的12例（33.3%）、14例其他脑部疾病患者中的0例（0%）和54例其他癌症患者中的1例（1.9%）的血清中检测到针对SOX 6的IgG抗体。在来自37名健康个体的血清中，除了一名老年女性外，未检测到针对SOX 6的IgG应答。此外，Western blot和ELISA分析从胶质瘤患者的血清显示，DNA结合结构域，HMG框的SOX 6，可能是一个优势的IgG抗SOX 6的表位。RT-PCR和北方杂交结果显示，SOX 6基因在胶质瘤组织中的表达高于正常成人组织，睾丸组织中的表达低于正常成人组织。用抗SOX 6抗体进行的Western印迹分析表明，SOX 6蛋白在胶质瘤组织中表达，但在正常成人脑组织中不表达。用抗SOX 6抗体的免疫组织化学分析显示，所有分析的胶质瘤组织在肿瘤细胞中表达SOX 6，但在来自大脑皮质的非肿瘤组织中仅检测到少数SOX 6阳性细胞。总之，这些结果表明发育调节转录因子SOX 6在神经胶质瘤中异常表达，并被来自神经胶质瘤患者血清的IgG特异性识别。
To identify tumor antigens for glioma, a human testis cDNA library was screened by serological identification of antigens by recombinant expression cloning with sera from glioma patients. In this screening, the most frequently isolated antigen was SOX6, an Sry-related high-mobility group (HMG) box-containing gene. SOX6 is a transcriptional factor that is specifically expressed in the developing central nervous system and in the early stages of chondrogenesis in mouse embryos. IgG antibodies against SOX6 were detected in sera from 12 of 36 glioma patients (33.3%), 0 of 14 patients with other brain disease (0%), and one of 54 other cancer patients (1.9%). In sera from 37 healthy individuals, no IgG responses against SOX6 were detected, except in an elderly female. Furthermore, Western blot and ELISA analyses with sera from glioma patients revealed that the DNA-binding domain, the HMG box of SOX6, might be a dominant epitope of IgGs against SOX6. RT-PCR and Northern blot analysis revealed that the SOX6 gene was more highly expressed in glioma tissues than in normal adult tissues, except testis. Western blot analysis with an anti-SOX6 antibody demonstrated that the SOX6 protein was expressed in glioma tissues, but not in normal adult brain tissue. Immunohistochemical analysis with the anti-SOX6 antibody showed that all the glioma tissues analysed expressed SOX6 in tumor cells, but only a few SOX6-positive cells were detected in non-neoplastic tissues from the cerebral cortex. In summary, these results indicate that the developmentally regulated transcription factor SOX6 is aberrantly expressed in glioma and specifically recognized by IgGs from glioma patients' sera.