論文名稱:

MKP-4於口腔鱗狀上皮癌細胞之角色

 

The roles of MKP-4 in oral squamous cell carcinoma cells

研究生:

劉碩典  Shuo-Tien Liu

指導教授:

張國威  Kuo-Wei Chang

        學位類別:

碩士

        學校名稱:

國立陽明大學

系所名稱:

口腔生物研究所

            學號:

39417007

          學年度:

95

          語文別:

中文

          出版年:

96

關鍵字:

口腔鱗狀上皮癌細胞  MKP-4

 

雙重特性去磷酸化酶  OSCC

 

  OECM-1

 

  SAS

摘要:

Mitogen-activated protein kinase (MAPK) 為細胞訊息傳遞的

 

重要路徑之一,負責細胞生長和分化等扼要的功能。因此MAPK需被嚴謹地調控。MAPK phosphatase (MKP) MAPK訊息傳遞中的調控者,其功能為將MAPK去磷酸化,即阻斷了MAPK的訊息傳遞。MKP-4MKP家族一員,又名dual specificity protein phosphatase (DUSP)-9,作用對象為p38 MAPK。先前在實驗室研究發現顯示在有抑制腫瘤細胞生長的類胰島素生長因子的結合蛋白第5 (IGFBP-5) 的細胞裡,其MKP-4的表現量有下降的現象。所以推測MKP-4與腫瘤的生成有關係,即鎖定其為本次研究的目標。建構帶有MKP-4基因之質體,並轉染至OECM-1SAS兩株口腔癌細胞,可順利在細胞中表現MKP-4,而且細胞之p38 MAPK之活性降低。轉染後,實驗發現MKP-4可以促進OECM-1SAS兩株口腔癌細胞的生長 (proliferation) 與移行 (migration),但不會影響非貼附性生 (anchorage-independence growth),此生長與移行之促進或可助長腫瘤發展。而實驗結果也發現MKP-4是透過 p38 MAPK活性降低造成此生長與移行之促進。

   
 

Mitogen-activated protein kinase (MAPK) pathway is one of the most important cell signaling pathway. Many crucial cellular activities are controlled by the MAPK pathways including cell proliferation, differentiation, and apoptosis. This is also the reason for MAPK pathway needs to be tightly regulated. MAPK phosphatases (MKPs) are dual specificity phosphatases that able to remove the phosphor group of activated MAPK. MKP-4 , known as dual-specificity phosphatase-9, belongs to the MKP family and is characterized to dephosphorylate p38 MAPK. Previous study In our laboratory showed the expression level of MKP-4 was decreased in the oral squamous cell carcinoma (OSCC) cell line that transient expressing Insulin-like growth factor binding protein (IGFBP) -5, a tumor suppressor found by our laboratory. Further investigation of the relation between MKP-4 and OSCC is the main target of this research. A MKP-4 expressing plasmid was constructed and transfected into OECM-1 and SAS OSCC cell lines. Cells expressed high MKP-4 had inactivation of p38 MAPK. The phenotypes of cell proliferation, migration, and anchorage-independence growth were observed after the transfection. As a result, MKP-4 induced cell proliferation and migration of both OECM-1 and SAS, but not anchorage-independence growth. The induction of proliferation and migration may enhance the development of neoplasms. Experiment results also showed MKP-4 causes the enhancement of OSCC proliferation and migration through p38 MAPK inactivation.

        論文目次:

中文摘要•••••••••••••••••••••••1

 

英文摘要•••••••••••••••••••••••2

 

緒論•••••••••••••••••••••••••3

 

研究目的•••••••••••••••••••••••13

 

實驗材料與方法••••••••••••••••••••14

 

實驗結果•••••••••••••••••••••••28

 

討論•••••••••••••••••••••••••35

 

圖表•••••••••••••••••••••••••39

 

參考資料•••••••••••••••••••••••52

 

附圖•••••••••••••••••••••••••56

 

附表•••••••••••••••••••••••••58