Expression of targeting protein for Xklp2 associated with both malignant transformation of respiratory epithelium and progression of sguamous cell lung cancer
Expression of targeting protein for Xklp2 associated with both malignant transformation of respiratory epithelium and progression of sguamous cell lung cancer
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DOI：
10.1158/1078-0432.ccr-05-1766
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发表时间：
2006-02-15
影响因子：
11.5
通讯作者：
Gao, YN
中科院分区：
文献类型：
--
作者：
Ma, Y;Lin, DM;Gao, YN
目的：微管相关蛋白Xklp 2（TPX 2）的靶向蛋白的表达受细胞周期的密切调控。TPX 2在多种恶性肿瘤中的异常表达已有报道，但在肺癌中的表达较少。本研究探讨TPX 2异常表达在人肺鳞癌发生发展中的意义。实验设计和结果：TPX 2在肺癌组织中的表达情况（L、PAa和PG）和永生化支气管上皮细胞（C45、M-BE、Tr和Y-BE）细胞系中，并分别通过逆转录-PCR和蛋白质印迹法在RNA和蛋白质水平上检测TPX 2的表达。免疫荧光染色显示TPX 2蛋白在分裂间期位于细胞核内，在分裂中期位于纺锤体内。对114例肺癌癌前病变和432例鳞癌组织进行免疫组化分析。在正常支气管上皮和肺泡中发现极低水平的TPX 2蛋白，而在鳞状上皮化生、异型增生、原位癌和浸润性肿瘤组织中观察到逐渐增加的TPX 2蛋白水平。统计学分析显示，TPX 2免疫组化标记指数与肺鳞癌的分化程度、分期及淋巴结转移有关，TPX 2过表达与患者5年生存率下降显著相关。TPX 2的异常表达可能起重要作用。在呼吸道上皮恶性转化和鳞状细胞肺癌的进展中，可以作为疾病的预后预测因子。
Purpose: Expression of targeting protein for Xklp2 (TPX2), a microtubule-associated protein, is tightly cell cycle regulated. Abnormally expressed TPX2 has been reported in various malignancies, but less is known in lung cancer. The present study appraised the significance of TPX2 aberrant expression for tumorigenesis and progression of human squamous cell carcinoma (SCC) in lung.Experimental Design and Results: The expressive status of TPX2 was firstly examined with lung cancer (L, PAa, and PG) and immortalized bronchial epithelial (C45, M-BE, Tr, and Y-BE) cell lines, and TPX2 expression was detected at both RNA and protein levels by reverse transcription-PCR and Western blotting, respectively. Immunofluorescence staining on M-BE cells showed that the subcellular localization of TPX2 protein is in nucleus at interphase and mitotic spindle at metaphase. Immunohistochemical analyses were subsequently done on the precancerous lesions derived from 114 patients and the tumor tissues of 432 patients with SCC in lung. Extremely low levels of TPX2 protein were found in the normal bronchial epithelia and alveoli, whereas gradually increased TPX2 protein levels were observed in the squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor tissues. Statistical analysis showed that the TPX2 immunohistochemistry labeling index was correlated with the differentiation grade, stage, and lymphous metastasis of SCC in lung and that TPX2 overexpression is significantly associated with decreased 5-year survival rate of the patients.Conclusions: Aberrant expression of TPX2 may play important role(s) in both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer and could serve as a prognostic predictor for the disease.