Tsai Sen-Tien, Yang Kai-Ying, Jin Ying-Tai, Lin Yen-Chun, Chang Mei-Tzu, Wu Li-Wha
Department of Otolaryngology, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 70428, Taiwan, ROC.
Oral Oncol. 2006 Apr;42(4):381-90. doi: 10.1016/j.oraloncology.2005.09.005. Epub 2005 Dec 20.
Amphiregulin (AR), an epidermal growth factor (EGF)-like molecule, is a mitogen for keratinocytes. Squamous cell carcinoma (SCC) is a tumor derived from keratinoctyes. Expression of AR mRNA positively correlated with the clinical progression of 39 oral SCC. Oral SCC line, KB, was used as a model to study if increased expression of AR altered the biological behaviors of SCC cells. Exogenous AR dose-dependently enhanced the proliferation of KB cells expressing EGF receptor 1 (EGFR-1), a major receptor for AR, but little AR. Neutralizing anti-AR antibody significantly reversed the stimulatory effect of exogenous AR on KB cell proliferation. Ectopically expressed AR in stable clones manifested higher abilities to proliferate, migrate and invade Matrigel than vector control. Cyclooxygenase 2 (COX-2), but not metalloprotease 9 (MMP-9) mRNA, was increased in all the AR-expressing stable clones. In summary, AR behaves as a tumor promoter for oral SCC cells partly via increased expression of COX-2.
双调蛋白（AR）是一种表皮生长因子（EGF）样分子，是角质形成细胞的促有丝分裂原。鳞状细胞癌（SCC）是一种源自角质形成细胞的肿瘤。AR mRNA的表达与39例口腔SCC的临床进展呈正相关。口腔SCC细胞系KB被用作模型，以研究AR表达增加是否会改变SCC细胞的生物学行为。外源性AR剂量依赖性地增强了表达EGF受体1（EGFR-1）的KB细胞的增殖，EGFR-1是AR的主要受体，但AR作用微弱。中和抗AR抗体显著逆转了外源性AR对KB细胞增殖的刺激作用。在稳定克隆中异位表达的AR表现出比载体对照更高的增殖、迁移和侵袭基质胶的能力。在所有表达AR的稳定克隆中，环氧合酶2（COX-2）的mRNA水平升高，而金属蛋白酶9（MMP-9）的mRNA水平未升高。总之，AR部分通过增加COX-2的表达而表现为口腔SCC细胞的肿瘤促进因子。
