Department of Oral and Maxillofacial Surgery, College of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
Biotechnol Lett. 2013 Sep;35(9):1377-85. doi: 10.1007/s10529-013-1213-7. Epub 2013 May 21.
Over-expression of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1) plays a crucial role in the formation of pleomorphic adenoma, which is the most common type of salivary gland tumor. To understand the molecular mechanisms governing PLAG1-mediated tumorigenesis, we used a microarray-based approach to identify PLAG1 target genes. We validated the expression of several genes, including Bax, Fas, p53, p21, p16, Cyclin D1, Egfr, Trail-R/DR5, c-Fos, c-myc and Igf2, by real-time RT-PCR or western blotting. Using luciferase reporter gene assays, we determined that the promoters of Bax, Fas, p53, TRAIL-R/DR5, and c-Fos were transactivated by PLAG1. PLAG1 not only activates genes that promote cell proliferation and tumor formation but also genes that inhibit these cellular processes. Therefore, we conclude that PLAG1 may play a dual role in tumor formation.
原癌基因多形性腺瘤基因 1(PLAG1)的过度表达在多形性腺瘤的形成中起着关键作用,多形性腺瘤是最常见的唾液腺肿瘤。为了了解调控 PLAG1 介导的肿瘤发生的分子机制,我们使用基于微阵列的方法来鉴定 PLAG1 靶基因。我们通过实时 RT-PCR 或 Western blot 验证了包括 Bax、Fas、p53、p21、p16、Cyclin D1、Egfr、Trail-R/DR5、c-Fos、c-myc 和 Igf2 在内的几个基因的表达。通过荧光素酶报告基因检测,我们确定 Bax、Fas、p53、TRAIL-R/DR5 和 c-Fos 的启动子被 PLAG1 转录激活。PLAG1 不仅激活促进细胞增殖和肿瘤形成的基因,还激活抑制这些细胞过程的基因。因此,我们得出结论,PLAG1 可能在肿瘤形成中发挥双重作用。