口腔癌致癌基因之探討

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Title:	口腔癌致癌基因之探討 The Study of the Potential Molecular Targets in Oral Squamous Cell Carcinoma
Authors:	王姿淑;Tzu-Shu Wang
Contributors:	生命科學院生物科技學系碩士班
Keywords:	口腔癌;OSCC;WWP1
Date:	2010
Issue Date:	2010-09-29 12:06:36 (UTC+8)
Abstract:	衛生署近年來的統計資料顯示，口腔癌在台灣地區的發生率和死亡率有逐步上升的趨勢，目前已知外在環境因子，如：抽菸、喝酒、嚼食檳榔等刺激，可能造成染色體上特定之基因變異，而基因體變異與口腔癌的發生有密切的關係，因而探討致癌因子所導致的基因體變異是目前研究口腔癌主要的方向。 WW domain containing E3 ubiquitin protein ligase 1 (WWP1)為一個近年來新發現的潛在致癌基因，先前的研究證實，WWP1在前列腺癌及乳癌中皆呈現基因增幅和過度表現的情形，並指出WWP1會促進癌細胞的增生並抑制細胞凋亡。本實驗室先前亦發現，WWP1在口腔癌細胞及組織中基因增幅和過度表現的情形。因此本研究延續先前之結果，探討WWP1的大量表現在口腔癌形成中所扮演的角色，我們利用病毒干擾性核醣核酸技術抑制口腔癌細胞中WWP1之表現，結果顯示，WWP1之mRNA及蛋白質表現明顯下降，接著再進行細胞計數與MTT assay檢測細胞生長情形，發現細胞之形態發生改變且生長受到抑制，進一步對照流式細胞儀的分析，發現細胞週期在S期停滯，而處於sub-G1細胞之比例明顯上升，且有細胞凋亡的現象產生並造成細胞死亡。因此綜合以上的結果，我們初步證實了WWP1為致癌基因，WWP1的過度表現將使得口腔癌細胞大量增生並抑制細胞凋亡。 The mortality of oral squamous cell carcinoma (OSCC) is one of the 10 leading causes of cancer deaths in Taiwan. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for OSCC. Our laboratory has found that WW domain containing E3 ubiquitin protein ligase 1 (WWP1) overexpressed in OSCC due to gene amplification. WWP1 belongs to the C2-WW-HECT type E3 family, and the involvement of the HECT-type E3s in crucial signaling pathways implicates in tumorigenesis. The amplification and overexpression of WWP1was also found in prostate cancer and breast cancer. Knockdown of WWP1 suppressed cell proliferation and induced apoptosis. These finding suggest an oncogenic role of WWP1 in carcinogenesis. In this study, we investigated the functional roles of WWP1 in OSCC with RNA interference using VSV-G pseudotyped lentivirus system. To verify the RNAi-induced expression, we examined WWP1 mRNA and protein expression by real time RT-PCR and Western blotting. Inhibition of cell growth was examined by trypan blue counting and MTT assay. The effects on cell cycle phase and apoptosis were determined by flow cytometry. Our findings showed that knockdown of WWP1 would cause cell cycle arrest in S phase and induce apoptosis in OSCC cell line. These results suggest that genomic aberrations of WWP1 may contribute to the pathogenesis of OSCC.
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