根據民國九十一年行政院衛生署的統計資料顯示，口腔癌為台灣男性十大癌症死因的第五位。在台灣，導致口腔癌的主要原因為嚼食檳榔。因此，本研究的目的在針對自倉鼠動物模式中發現的一個口腔腫瘤抑制候選基因CDK2AP1進行研究，探討其表現量與口腔癌之間的相關性。人類口腔腫瘤抑制候選基因CDK2AP1為一個長度為1.6 Kbp的基因，位於人類染色體12q24.31，轉釋出的蛋白質分子量大小為12.4kDa。就蛋白質功能而言，人類CDK2AP1蛋白質會與DNA polymerase α/primase產生交互作用，進而對DNA的複製產生負向調控的作用。也有研究指出，在微衛星(microsatellite)不穩定的大腸癌細胞株裡面，發現CDK2AP1蛋白質的表現量有減少或降低的趨勢，這個發現證明由大腸惡性腫瘤細胞轉變成大腸癌細胞，CDK2AP1蛋白質的表現量減少或降低是一個重要的特徵與指標。在口腔癌開始癌化或是癌化過程中，CDK2AP1基因所扮演的角色，並不明確。因此，本研究主要是要選殖CDK2AP1基因完整的cDNA (CDs)並探討其和口腔癌之間的相關性。首先，從50口腔癌病人的組織上萃取其RNA然後轉成cDNA，接著，我們從胃癌的細胞珠(Scm1)選殖出CDK2AP1基因完整的cDNA，接著我們再把選殖出來的CDK2AP1 cDNA轉接入具有表現蛋白質的不同載體上面，藉以檢視CDK2AP1蛋白質在細胞的表現位置，並進一步製備CDK2AP1的抗體進行口腔癌組織及口腔癌組織切片CDK2AP1蛋白表現之分析和探討其對DNA的調控功能為何。實驗結果顯示，藉由免疫螢光染色的技術，我們已經證明CDK2AP1蛋白質主要表現在細胞核與細胞質的位置。另外藉由即時定量PCR分析，我們也建立口腔癌組織中CDK2AP1 mRNA的表現量變曲線。經由即時定量PCR的分析結果顯示，在mRNA的表現層面上，CDK2AP1 mRNA的表現量在口腔癌的組織表現的較正常的口腔組織還要來的高。此外，藉由西方點墨法和免疫組織染色的分析，我們也證明和比對CDK2AP1蛋白質在口腔癌組織與正常口腔組織的表現量狀況。實驗結果顯示，藉由西方點墨法和免疫組織染色的分析方法所得的結果與即時定量PCR分析所得的結果是相同的，也就是在蛋白質的表現層次上，CDK2AP1蛋白質的表現量在口腔癌的組織上其表現量是比正常的口腔組織還要來的高。

Oral squamous cell carcinoma (OSCC) is now the forth leading cause of male cancer mortality in Taiwan. The betel quid (BQ) chewing is the main cause OSCC in Taiwan. This study was aimed to clone the CDK2-associated protein 1 (CDK2AP1) complete CDs and characterization of its expression profiles as well as protein sublocalization in oral cancers. The human CDK2AP1 gene is 1.6 Kbp in length, mapped to 12q24.31 and encodes for a 12.4 kDa polypeptide. Human CDK2AP1 protein interacts with DNA polymerase alpha/primase resulting in negative regulation of the rate of initiation of DNA replication. It has been reported that differential CDK2AP1 expression, with decreased or absent expression in microsatellite-unstable (MSI+) colorectal cancer (CRC) cell lines, suggesting that loss of CDK2AP1 protein expression is a characteristic of malignant transformation in MSI+CRC. The role of CDK2AP1 in the onset or progression of oral cancer is still unknown. In this study, we firstly extracted RNA from 45 patients’ specimens. Then, we cloned CDK2AP1 CDs from stomach carcinoma cell line (Scm1) and subcloned into various protein expression vectors for further examining CDK2AP1 subcellular localization in HeLa cell. Polyclonal CDK2AP1 antibody was prepared. We have demonstrated that the CDK2AP1 protein locates in both cytoplasm and nucleus by immunofluorescence analysis. In addition, we examined the CDK2AP1 mRNA expression profiles in oral cancer specimens by quantitative RT-PCR. The results showed that the expression of CDK2AP1 mRNA in oral cancer tissues were higher than those in normal oral tissues. Furthermore, we have determined and compared the CDK2AP1 protein in both oral cancer and normal tissues by immunoblotting analysis and immunohistochemical (IHC) analysis. The results from both immunoblotting and IHC were consistent with the results from quantitative RT-PCR. CDK2AP1 protein expression was higher in oral cancer tissues than in normal oral tissues.

Abstract
chinese．．．．．．．．．．．．．．．．．．．．．．．．．I
English．．．．．．．．．．．．．．．．．．．．．．．．III
Abbreviations．．．．．．．．．．．．．．．．．．． ．．IV
Chapter 1. A Review of Oral Cancer．．．．．．．． ．．．1
Chapter 2. Materials and Methods．．．．．．．．．．．．13
Chapter 3. Results．．．．．．．．．．．．．．．．．．．30
Chapter 4. Discussion．．．．．．．．．．．．．．．． ．37
References．．．．．．．．．．．．．．．．． ．．．．． 41
Tables．．．．．．．．．．．．．．．．．．．．．．．．．56
Figures．．．．．．．．．．．．．．．．．．．．．．．． 58
Appendix．．．．．．．．．．．．．．．．．．．．．．．．74

行政院衛生署 (2003) 台灣地區主要癌症死亡原因。http://www.doh.gov.tw/NewVersion/index.asp
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