出版年:

研究生:

胡立安

研究生(英文姓名):

Li-An Hu

論文名稱:

研究肝癌細胞及肝組織中Fas和FasL基因的表現

英文論文名稱:

Study on the expressions of Fas and FasL genes in hepatoma cells and hepatic tissues

指導教授:

葉才明 ; 楊倍昌

指導教授(英文姓名):

Trai-Ming Yeh ; Bei-Chang Yang

學位類別:

碩士

校院名稱:

國立成功大學　

系所名稱:

微生物暨免疫學研究所

學號:

S46861107

學年度:

87

語文別:

中文

論文頁數:

51

關鍵詞:

肝癌

英文關鍵詞:

Fas ; FasL

被引用次數:

0

[ 摘要 ]

Fas傳遞系統是由Fas為接受器(receptor)和為與Fas接合的Fas-ligand (FasL)所組成。當FasL 連結到Fas時，表現Fas的細胞則會走向死亡，此種現象參與體內很多重要的生理過程。
Fas和FasL都是屬於腫瘤壞死因子接受器/神經生長因子接受器的一員。最近的研究報告顯示，腫瘤可能會利用表現功能性FasL主動殺死入侵的免疫細胞，稱為"反攻擊模式"。 除此之外，腫瘤細胞還可能失去Fas傳遞訊號的功能，以逃避免疫系統的攻擊。本研究運用反轉錄聚合連鎖反應、流體細胞免疫螢光分析儀和西方墨點法偵測四株肝癌細胞株和肝組織上Fas和FasL的表現及其功能，以瞭解肝癌細胞逃避免疫偵察的機制。結果顯示，HepG2、Huh7和PLC/PRF/5三株細胞同時表現Fas和FasL，然而Hep3B則不表現Fas只有FasL。在組織方面，肝癌組織檢體之腫瘤和非腫瘤部分，都可能同時表現Fas和FasL。另外，四株肝癌細胞經Fas抗體處理後，Fas訊號傳遞皆被活化，但細胞卻不會死亡。而在共培養實驗中顯示肝癌細胞皆能造成Jurkat細胞死亡，但是可能不是因肝癌細胞上的FasL直接引起。不同的肝癌細胞株表現的抗細胞凋亡的基因bcl-2、 bcl-x 和FAP-1不盡相同。總結以上結果推測，肝癌細胞株可能不僅只阻斷Fas/FasL路徑，亦會利用其它的方式來逃避免疫系統的攻擊。

[ 英文摘要 ]

The Fas signaling system, comprising the Fas receptor (Fas) and its ligand, Fas ligand (FasL), is one of the mediators of programmed cell death found in various physiological and pathological processes. After engagement of FasL with Fas, apoptotic signal will be transmitted into Fas-bearing cells. Recently, a variety of tumors have been shown to express functional FasL and that may be involved in immune escape. In addition, dysfunction in Fas signaling was observed in human hepatocellular carcinoma (HCC), which may be an additional mechanism in tumor escape. To explore further the mechanisms of immune escape by HCC, we applied RT-PCR, flow cytometry, and Western blot to measure the expression of Fas and FasL in hepatoma cells and tumor tissues. HepG2, Huh7 and PLC/PRF/5 expressed both Fas and FasL genes. We did not detect the expression of Fas in Hep3B cells, although FasL was expressed in this cell line. Tissues of hepatic tumor and nontumor part expressed both Fas and FasL to various levels. In addition, we demonstrated that hepatoma cell lines induced Jurkat T cell apoptosis, but this may be not mediated through Fas/FasL pathway. By contrast, all the hepatoma cell lines resisted to Fas antibody-induced apoptosis, although the Fas signaling was activated in those Fas-bearing cells. Several anti-apoptoic genes such as bcl-2, bcl-x or FAP-1 were detected in hepatoma cell lines as well as in hepatic tissues to various levels. Collectively, these results suggested that hepatoma cells may escape immune attack by down-regulation of Fas as well as other pathways such as overexpression of anti-apoptosis related genes.