Breuer Roderick H J, Snijders Peter J F, Smit Egbert F, Sutedja Thomas G, Sewalt Richard G A B, Otte Arie P, van Kemenade Folkert J, Postmus Pieter E, Meijer Chris J L M, Raaphorst Frank M
Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
Neoplasia. 2004 Nov-Dec;6(6):736-43. doi: 10.1593/neo.04160.
Polycomb group (PcG) genes are responsible for maintenance of cellular identity and contribute to regulation of the cell cycle. Recent studies have identified several PcG genes as oncogenes, and a role for PcG proteins in human oncogenesis is suspected. We investigated the expression of BMI-1 and EZH2 PcG oncogenes in human bronchial squamous cell carcinomas (SCCs) and bronchial premalignant precursor lesions (PLs). Whereas normal bronchial epithelium was associated with widespread expression of BMI-1 in resting EZH2-negative cells, neoplastic cells in lung carcinomas displayed altered expression of both BMI-1 and EZH2. Two patterns of abnormal PcG expression were observed: increased expression of BMI-1 in dividing neoplastic cells of PLs and SCCs, and enhanced expression of EZH2 and Ki-67 in BMI-1-positive cells according to severity of the histopathologic stage. We propose that altered expression of BMI-1 and EZH2 is an early event that precedes high rates of proliferation in lung cancer. Because PcG complexes are normally involved in the maintenance of cell characteristics, abnormal PcG expression may contribute to loss of cell identity.
多梳蛋白家族（PcG）基因负责维持细胞特性，并参与细胞周期调控。最近的研究已将多个PcG基因鉴定为癌基因，人们怀疑PcG蛋白在人类肿瘤发生中发挥作用。我们研究了BMI-1和EZH2这两种PcG癌基因在人支气管鳞状细胞癌（SCC）和支气管癌前病变（PL）中的表达情况。正常支气管上皮与静止的EZH2阴性细胞中广泛表达的BMI-1相关，而肺癌中的肿瘤细胞则显示BMI-1和EZH2的表达均发生改变。观察到两种异常的PcG表达模式：PL和SCC的增殖肿瘤细胞中BMI-1表达增加，以及根据组织病理学分期的严重程度，BMI-1阳性细胞中EZH2和Ki-67表达增强。我们认为，BMI-1和EZH2表达改变是肺癌高增殖率之前的早期事件。由于PcG复合物通常参与细胞特性的维持，异常的PcG表达可能导致细胞特性丧失。
