| 摘要: | 在台灣地區，口腔癌的發生率以及致死率都高居癌症死因排名前十名。由於過去口腔癌之基因體變異研究甚少，因此，本研究應用微陣列比較基因體雜合術(aCGH)，針對10對成對臨床口腔癌樣本進行分析。結果發現在染色體1p、3q、7p、8q、9、11q、16、17、19、20和22呈現基因套數增幅(amplification)；相對地，在染色體3p、4q、5q、8p、10、18q和Y則呈現基因套數刪除(deletion)。先前的文獻發現，染色體8q21上的WWP1基因在乳癌和前列腺癌是潛在致癌基因。根據aCGH的結果發現，在10對口腔癌組織中，有80％呈現WWP1 基因套數增幅，因此，我們更進一步利用即時定量聚合酶反應（Q-PCR）來分析更多口腔癌檢體以及口腔癌細胞株，了解WWP1 的基因異常情形。結果顯示，在口腔癌檢體中，有39％(23/59)呈現WWP1 的基因套數增幅；有35％(16/46)呈現WWP1 的基因過度表現，經由臨床病理資料交叉比對，與病理資料尚無顯著相關。應用免疫組織染色法偵測18對成對口腔癌樣本WWP1蛋白表現，發現不同的樣本呈現不同的蛋白表現量，表現在細胞的位置也有所不同。在細胞株中，WWP1基因套數、基因表現和蛋白表現，在不同的口腔癌細胞株呈現不同的表現趨勢。本研究首度探討WWP1基因在口腔癌細胞株和臨床樣本中所扮演的角色，結果發現WWP1基因增幅可能與口腔癌的發生有關。
Oral Squamous Cell Carcinoma(OSCC) is the sixth of common death carcinoma in Taiwan. In the past, the research of genomic variation in OSCC is rare, so in the study we used a genome-wide array comparative genomic hybridization (aCGH) technology to assess 10 OSCC patients for detailed analysis of genomic aberration that may play a role in the development and progression of oral cancer. Our aCGH results revealed DNA copy number amplification on chromosome 1p, 3q, 7p, 8q, 9, 11q, 16, 17, 19, 20 and 22, as well as DNA copy number deletion on chromosome 3p, 4q, 5q, 8p, 10, 18q and Y. In particular, we found on WWP1, located at chromosome 8q21, which has been proposed to be an oncogene for breast cancer and prostate cancer. WWP1 is a ubiquitin ligase associated with the post-translational regulation of oncoproteins and tumor suppressor proteins. Our aCGH results revealed 80％ WWP1 DNA copy number amplification. In accordance with WWP1 copy number change and mRNA expression in OSCC clinical samples and cell lines, we applied Q-PCR technology to confirm our data. Our results showed that 39% of 59 OSCC clinical DNA samples represent WWP1 amplification, 35% of 46 OSCC clinical RNA samples represent WWP1 overexpression. To analyze WWP1 protein expression in clinical samples, we applied IHC technology to detect the level of WWP1 protein in 18 paired OSCC samples, our data represented different they had different protein pattern and location. In OSCC cell lines, WWP1 copy number change had different tendency with mRNA, protein expression. For the first time, we analyzed WWP1 in clinical OSCC samples and cell lines in this study, our data showed that WWP1 DNA amplification maybe associated with carcinogenesis of OSCC. |
