Chai Y, Peng B, Dai L, Qian W, Zhang Y, Zhang J-Y
Center for Tumor Biotherapy, The First Affiliated Hospital, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450052, China ; Department of Biological Sciences, The University of Texas at El Paso, 500 W. University Ave., El Paso, TX, 79968, USA.
Scand J Immunol. 2014 Nov;80(5):362-8. doi: 10.1111/sji.12202.
The human homologue of the mouse double minute 2 (MDM2) is known to be overexpressed in a variety of human malignancies. As one of E3 ubiquitin-protein ligases, MDM2 interacts with the tumour suppressor p53 by mediating ubiquitination and degradation of p53. Since abnormally expressed proteins can induce autoimmune response, to further examine whether sera from patients with esophageal squamous cell carcinoma (ESCC) exhibited immunoreactivity against MDM2 and p53, autoantibody responses to MDM2 and p53 were evaluated by enzyme-linked immunosorbent assay (ELISA) in sera from patients with ESCC and normal individuals. Positive results were also confirmed by Western blotting and indirect immunofluorescence assay. The results demonstrated that the positive rate of autoantibody against p53 and MDM2 in ESCC sera was 22.9% (36/157) and 14.0% (22/157), whereas this rate was 0% (0/85) and 1.2% (1/85), respectively, in normal individuals. Some of the sera with antibodies specific for MDM2 also contained antibodies against p53. And there was an increase of positive antibody reactions reaching a frequency of 35% (55/157) combination with MDM2 and p53. This was significantly higher than the frequency of antibodies in normal individuals (P < 0.01). Our preliminary results suggest that autoantibodies against MDM2 and p53 may be useful serum biomarkers in the immunodiagnosis of ESCC.
已知小鼠双微体2（MDM2）的人类同源物在多种人类恶性肿瘤中过表达。作为E3泛素蛋白连接酶之一，MDM2通过介导p53的泛素化和降解与肿瘤抑制因子p53相互作用。由于异常表达的蛋白质可诱导自身免疫反应，为进一步检测食管鳞状细胞癌（ESCC）患者血清是否对MDM2和p53表现出免疫反应性，采用酶联免疫吸附测定（ELISA）对ESCC患者和正常个体血清中针对MDM2和p53的自身抗体反应进行了评估。Western印迹法和间接免疫荧光测定法也证实了阳性结果。结果表明，ESCC患者血清中抗p53和抗MDM2自身抗体的阳性率分别为22.9%（36/157）和14.0%（22/157），而正常个体的这一比率分别为0%（0/85）和1.2%（1/85）。一些对MDM2具有特异性抗体的血清中也含有抗p53抗体。MDM2和p53抗体反应阳性率增加，达到35%（55/157）。这显著高于正常个体中抗体的频率（P<0.01）。我们的初步结果表明，抗MDM2和抗p53自身抗体可能是ESCC免疫诊断中有价值的血清生物标志物。
