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Opposing functions of PLAG1 in pleomorphic adenoma: a microarray analysis of PLAG1 transgenic mice
Authors:Yang Wang  Wenjun Shang  Xia Lei  Shukun Shen  Hongxin Zhang  Zhugang Wang  Lei Huang  Zhiwei Yu  Huishan Ong  Xuelai Yin  Wenjun Yang  Chenping Zhang
Institution:1. 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
2. Laboratory of Oral Tumor and Oral Biology, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, 200011, People’s Republic of China
3. Model Organism Division, Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
Abstract: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.
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