透過您的圖書館登入
IP:3.133.120.10
  • 學位論文

分析蛋白激酶C在人類肝癌細胞之表現

Analyzing the Expression of Protein Kinase C Family in Human Hepatocellular Carcinoma

指導教授 : 周芬碧

摘要


蛋白激酶C( Protein kinase C; PKCs)在細胞增殖、分化、凋亡、遷移、促進腫瘤等方面都扮演重要角色,在本研究中我們分析人類肝癌細胞之多種PKC表現狀況,利用即時定量反轉聚合酵素鏈鎖反應(real-time quantitative RT-PCR)、突變分析及免疫組織染色調查50對肝癌細胞PKC η蛋白質的表現,試圖探索肝癌發展過程它們可能扮演的角色,結果顯示PKC β 及PKC θ在肝癌組織中被負調節表現量降低,經分析比對,PKC θ低表現量與癌細胞分級有關(p=0.009),而PKC βII低表現量與B型肝炎感染有關 (P=0.035),其相關性具統計學意義,這些分析結果顯示PKC β 及PKC θ表現量在肝癌發展過程具有臨床重要性。另外我們也發現有82%肝癌組織的PKC η蛋白質被負調節,此蛋白量降低的現象與肝癌病人低存活率相關,由此實驗結果可以推測PKC η蛋白質在肝癌發展過程中扮演腫瘤抑制的角色。

並列摘要


Protein kinase Cs(PKCs) play important roles in cell proliferation, differentiation, apoptosis, migration and tumorigenesis. In the present study, we analyzed the expression of PKCs in human hepatocellular carcinoma (HCC) tissues and explored their roles in the development of HCC., we used real-time quantitative RT-PCR, mutation analysis, and immunohistochemical staining to investigate the expression of PKCs in 50 pairs of human hepatocellular carcinoma (HCC) tissues. Results showed that PKC β and PKCθ were down-regulated in HCC tissues. Reduced expression of PKC θ is well correlated with the grade of cancer cells (p=0.009), and the down-regulated expression of PKC βII is associated with HBV infection (P=0.035). From these results, we suggest that the expression of PKC θ and PKC β may have clinical significance in HCC. Specialy, our data showed that the expression of PKCη is down-regulated in 82% of HCC tissues. The down-regulation is associated with poorer long-term survival of HCC patients. These results suggest that PKC η plays a tumor suppressor-like role in the development of HCC.

參考文獻


1.Beasley RP, Huang LY, Lin C and Chien C. Hepatocellular carcinoma and HBV: a prospective study of 22,707 men in Taiwan. Lancet 1981; 2: 1129-1133.
2.Mason WS, Aldrich C, Summer J and Taylor JM. Asymmetric replication of duck hepatitis B virus DNA in liver cells:Free minus strand DNA. Proc Natl Acad Sci USA 1982; 79:3997-4001.
3.Beasley RP. Hepatitis B virus:the major etiology for hepatocellular carcinoma. Cancer 1988; 61: 1942-1956.
4.Koshy R and Hofschneider PH. Transactivation by hepatitis B virus may contribute to hepatocarcinogenesis. Curr Topics Microbiol Immunol 1989; 144: 265-281.
5.Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, Groopman JD, Gao YT and Henderson BE. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992; 339:1413-1414.

延伸閱讀