Decreased PITX1 homeobox gene expression in human lung cancer
Decreased PITX1 homeobox gene expression in human lung cancer
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DOI：
10.1016/j.lungcan.2006.11.001
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发表时间：
2007-03-01
期刊：
影响因子：
5.3
通讯作者：
Petersen, Iver
中科院分区：
文献类型：
--
作者：
Chen, Yuan;Knoesel, Thomas;Petersen, Iver
PITX 1（垂体同源框1）基因在人类发育中具有重要作用，并被认为是各种癌症的肿瘤抑制因子。然而，在肺癌中PITX 1的作用仍有待阐明。在这项研究中，我们分析了PITX 1在mRNA和蛋白水平上在人肺癌中的表达。与正常人支气管相比，在癌细胞中发现PITX 1表达降低。通过北方印迹分析和RT-PCR以及Western印迹分析来检测HEBC和SAEC的细胞增殖。在原发性肺组织中，与正常肺组织相比，发现PITX 1 mRNA在大多数肿瘤中下调。观察到PITX 1 mRNA表达的缺乏与较高的肿瘤分级之间的关联。用免疫组化方法分析了135例原发性肺癌的组织芯片。84例（62%）PITX 1表达阴性，PITX 1表达水平越低，肿瘤分期越高。此外，发现肺癌细胞系H2228和H526在暴露于分化修饰剂5-溴脱氧尿苷（BrdU）后上调PITX 1。由于已知同源异型盒基因转录调节关键细胞过程，并与分化和癌变相关，我们认为PITX 1可能与肺癌的发展和进展有关。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The PITX1 (pituitary homeobox 1) gene has essential roles in human development and has been considered a tumor suppressor in various cancers. However, in tung cancer the role of PITX1 remains to be elucidated. In this study, we analyzed the expression of PITX1 at both mRNA and protein levels in human tung cancer. The reduced PITX1 expression was found in cancer cell tines test compared to normal human bronchial. epithelia cells (HEBC) and small airway epithelia cells (SAEC) by Northern blot analysis and RT-PCR as well as Western blot analysis. In primary lung tissues, PITX1 mRNA was found to be downregulated in the majority of tumors compared with normal lung tissues. An association between the lack of PITX1 mRNA expression and higher tumor grade was observed. A tissue microarray containing 135 primary lung carcinomas was analyzed by immunohistochemistry. Eighty-four cases (62%) exhibited no expression of PITX1 and the lower expression of PITX1 was significantly linked to higher tumor stages. Additionally, PITX1 was found to be upregulated in lung cancer cell lines H2228 and H526 after they were exposed to a differentiation modifying agent 5-bromodeoxyuridine (BrdU). Since homeobox genes are known to transcriptionally regulate key cellular processes and associated with differentiation and carcinogenesis, we suggest that PITX1 might be linked to lung cancer development and progression. (c) 2006 Elsevier Ireland Ltd. All rights reserved.