Expression of RACK1 is a novel biomarker in pulmonary adenocarcinomas
Expression of RACK1 is a novel biomarker in pulmonary adenocarcinomas
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DOI：
10.1016/j.lungcan.2009.09.015
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发表时间：
2010-07-01
期刊：
影响因子：
5.3
通讯作者：
Okayasu, Isao
中科院分区：
文献类型：
--
作者：
Nagashio, Ryo;Sato, Yuichi;Okayasu, Isao
为了开发有用的肺腺癌早期和/或鉴别诊断标志物，我们使用来自肺腺癌的A549细胞作为免疫原产生单克隆抗体。用amex固定和石蜡包埋的A549细胞制剂对杂交瘤上清液进行免疫组织化学筛选，以产生抗体。阳性克隆通过极限稀释进行两次单克隆。从一组获得的抗体中，一种被命名为KU-Lu-3的抗体显示细胞质染色。通过改良二维免疫印迹法检测KU-Lu-3识别的抗原，确定其为活化C激酶1 （activated C kinase 1, RACK1）受体。为了评估KU-Lu-3的有效性，我们使用福尔马林固定和石蜡包埋组织芯片切片对184例肺癌和配对的正常肺组织进行了免疫组织化学研究。在腺癌中表达频率高，在鳞状细胞癌和大细胞癌中很少表达（p < 0.0001）。此外，RACK1表达与腺癌患者的病理分期、肿瘤大小和淋巴结状况也有显著相关性，但与肿瘤分化、患者年龄和性别无关。这些结果提示RACK1可能是一种新的肺腺癌鉴别诊断标志物。2009爱思唯尔爱尔兰有限公司版权所有。
To develop useful early and/or differential diagnostic markers for pulmonary adenocarcinomas, we generated monoclonal antibodies using A549 cells derived from pulmonary adenocarcinomas as an immunogen. Hybridoma supernatants were immunohistochemically screened for antibody production by AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice by limiting dilutions. From a group of obtained antibodies, an antibody designated as KU-Lu-3 showed cytoplasmic staining. The antigen recognized by KU-Lu-3 was detected by modified two-dimensional immunoblotting, and was determined to be the receptor of activated C kinase 1 (RACK1). To evaluate the utility of KU-Lu-3, we immunohistochemically studied 184 cases of pulmonary carcinoma and paired normal lung tissues, using formalin-fixed and paraffin-embedded tissue microarray sections. The expression was significantly high and frequent in adenocarcinomas but was barely detected in a few squamous cell carcinomas and large cell carcinomas (p < 0.0001). Moreover, RACK1 expression was also significantly associated with the pathological stage, tumor size and lymph node status of adenocarcinoma patients, but not with tumor differentiation, or patient age and gender. These results suggest that RACK1 may be a novel differential diagnostic marker for pulmonary adenocarcinomas. (C) 2009 Elsevier Ireland Ltd. All rights reserved.