Chua Huey-Huey, Yeh Te-Huei, Wang Ying-Piao, Huang Yu-Tzu, Sheen Tzung-Shiahn, Lo You-Chang, Chou Ya-Ching, Tsai Ching-Hwa
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Number 1, Jen-Ai Road, Section 1, Taipei 10051, Taiwan, Republic of China.
Head Neck. 2008 Apr;30(4):427-36. doi: 10.1002/hed.20724.
Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and has high metastatic potential. Discoidin domain receptors (DDR1, DDR2) are receptor-type tyrosine kinases activated by collagen. Their ability to induce expression of matrix metalloproteinase is related with tumor invasion. Therefore, we aim to investigate DDRs gene expression and its regulation in NPC.
By use of real-time quantitative polymerase chain reaction (Q-PCR), DDR2 gene expression but not DDR1 was significantly higher in primary and metastatic NPC. DDR2 was predominantly distributed in NPC tumor cells rather than in infiltrating lymphocytes. EBV Z-transactivator (Zta) transfection may distinctly elevate DDR2 level. Furthermore, data from reporter assay indicate that Zta could transactivate DDR2 promoter activity, suggesting the possible upregulation mechanism.
DDR2 was differentially upregulated in NPC and modulated by EBV Zta protein. DDR2 may play a role in NPC invasion and serve as a diagnostic and therapeutic target.
鼻咽癌(NPC)与爱泼斯坦-巴尔病毒(EBV)相关,且具有高转移潜能。盘状结构域受体(DDR1、DDR2)是由胶原蛋白激活的受体型酪氨酸激酶。它们诱导基质金属蛋白酶表达的能力与肿瘤侵袭有关。因此,我们旨在研究DDRs基因在鼻咽癌中的表达及其调控。
通过实时定量聚合酶链反应(Q-PCR),DDR2基因在原发性和转移性鼻咽癌中的表达显著高于DDR1。DDR2主要分布于鼻咽癌肿瘤细胞而非浸润淋巴细胞中。EBV Z-反式激活因子(Zta)转染可明显提高DDR2水平。此外,报告基因检测数据表明Zta可反式激活DDR2启动子活性,提示可能的上调机制。
DDR2在鼻咽癌中差异上调,并受EBV Zta蛋白调控。DDR2可能在鼻咽癌侵袭中发挥作用,并可作为诊断和治疗靶点。