Liu Yan, Sun Wenyue, Zhang Kaitai, Zheng Hongwei, Ma Ying, Lin Dongmei, Zhang Xinyu, Feng Lin, Lei Wendong, Zhang Ziqiang, Guo Suping, Han Naijun, Tong Wei, Feng Xiaoli, Gao Yanning, Cheng Shujun
Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, PR China.
Lung Cancer. 2007 Jun;56(3):307-17. doi: 10.1016/j.lungcan.2007.01.016. Epub 2007 Feb 20.
To identify differentially expressed genes in lung squamous cell carcinomas (SCCs), the suppression subtractive hybridization method (SSH) was performed comparing six lung tumour tissues and 10 morphologically normal bronchial epithelial tissues. A cDNA library consisting of 220 upregulated genes in tumour tissue was established and named as LSCC (lung squamous cell carcinoma). Of them, six were tested using semi-quantitative reverse transcription-PCR on 27 pairs of tumour tissue and normal lung tissue. Differential expression was confirmed in five of these six genes, including IGFBP5, SQLE, RAP2B, CLDN1, and TBL1XR1. The elevated mRNA expression of RAP2B, CLDN1 and TBL1XR1, three genes located on chromosome 3q, were further validated in 64.3% (18/28), 82.1% (23/28), and 75.0% (21/28) of lung SCC tumour tissues, respectively, by quantitative real-time reverse transcription-PCR analysis. Moreover, western blot analysis showed that the protein expression of TBL1XR1 was also upregulated in 53.3% (8/15) of lung SCC tumour samples, as well as in five lung cancer cell lines and in one human immortalized bronchial epithelial cell line. All the initial characteristics of these genes were first reported in the lung SCCs. The differentially expressed genes reported in this study will provide a valuable resource for understanding the pathogenesis of lung SCCs and for discovery of novel diagnostic or therapeutic targets.
为了鉴定肺鳞状细胞癌(SCC)中差异表达的基因,采用抑制性消减杂交法(SSH),比较了6个肺肿瘤组织和10个形态学上正常的支气管上皮组织。建立了一个由肿瘤组织中220个上调基因组成的cDNA文库,并将其命名为LSCC(肺鳞状细胞癌)。其中,使用半定量逆转录PCR对27对肿瘤组织和正常肺组织中的6个基因进行了检测。这6个基因中有5个被证实存在差异表达,包括IGFBP5、SQLE、RAP2B、CLDN1和TBL1XR1。通过定量实时逆转录PCR分析,位于3号染色体上的RAP2B、CLDN1和TBL1XR1这三个基因的mRNA表达升高,在64.3%(18/28)、82.1%(23/28)和75.0%(21/28)的肺SCC肿瘤组织中分别得到进一步验证。此外,蛋白质印迹分析表明,TBL1XR1的蛋白质表达在53.3%(8/15)的肺SCC肿瘤样本中上调,在5个肺癌细胞系和1个人永生化支气管上皮细胞系中也上调。这些基因的所有初始特征均首次在肺SCC中报道。本研究中报道的差异表达基因将为理解肺SCC的发病机制以及发现新的诊断或治疗靶点提供有价值的资源。