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研究生:許拯源
研究生(外文):Cheng-yuan Hsu
論文名稱:鼻咽癌細胞處理MAPK抑制劑與黃體激素對誘發p57KIP2的影響
論文名稱(外文):The effects of MAPK inhibitor and progesterone on the induction of p57KIP2 in nasopharyngeal carcinoma cells
指導教授:卓忠隆
指導教授(外文):Chung-lung Cho
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:66
中文關鍵詞:鼻咽癌細胞週期訊息傳遞
外文關鍵詞:p57KIP2MAPKprogesterone
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鼻咽癌在西方相當罕見,然而在南中國卻是第三普遍的惡性腫瘤疾病,雖然已發現多種與鼻咽癌有密切關係的危險因子,如:遺傳、生活環境、EB病毒等,且隨著生活環境改善、治療方法不斷地進步,鼻咽癌患者的死亡率已逐漸降低。然而,直到目前,鼻咽癌形成的分子機制仍不是很清楚。
p57是調控細胞週期相關蛋白的Cip/Kip家族成員。p57基因在人類腫瘤中很少發生突變,顯示其功能的缺失主要起因於轉錄上或轉譯後表現受到了抑制。目前研究發現p57的功能缺失與多種發育缺陷和癌症的形成有關,如貝克維斯魏德曼症候群(BWS)、胃癌、膀胱癌等。由於訊息調控的研究大多集中在p21或是p27上,p57於生理上的表現和與細胞生長、基因的調控機制等的詳細機制都需要更進一步的特性分析研究。
科學家們對荷爾蒙與癌症間關聯性的研究已進行多年,由於鼻咽癌與荷爾蒙的相關研究非常的少,我們檢測數種荷爾蒙對鼻咽癌細胞的影響。結果發現其中progesterone與一MEK抑制劑-U0126有類似的作用機制,抑制了MAPK訊息傳遞分子的活化,且引發了p57的表現,並使得細胞生長受到抑制,細胞也停留在細胞週期的G1 phase;此外,在progesterone處理的同時加入其拮抗劑mifepristone (RU-486)後,抑制作用也受到了中和。因此,推論progesterone可能藉progesterone的receptor和MAPK訊息傳遞途徑調控p57的表現,來影響鼻咽癌細胞的細胞週期進行與生長。
Nasopharyngeal carcinoma (NPC) occurs occasionally in the west but is popular in south-eastern China and Hong Kong where it is the third most common form of malignancy among ethnic Chinese people. The possibly relevant factors associated with NPC have been found, for example, environment, genetics and EB virus, etc. Recently, as a result of improved environment of living and therapies, the death rate of NPC is decreasing year by year. However, the molecules mechanism underlying its tumorigenicity is still unclear.
The p57 protein is a maternally expressed, paternally imprinted cyclin-dependent kinases inhibitor (CDI). p57 mutations are rare in the human cancers, suggesting that other mechanisms of transcriptional or post translational silencing are involved in the loss of p57 function. Decreased expression of p57 has been found in Beckwith-Wiedemann syndrome (BWS), gastric cancer and bladder carcinoma. So far, many studies in signal transduction have been focused on p21 or p27. The relationship between p57 expression and signal transduction and cell proliferation under physiological circumstances requires further exploration.
Studies of the relationship between hormones and cancers have been proceeded for years, nevertheless, there is few about NPC. We examined several hormones’ effect on the NPC cell lines. We found that in response to progesterone treatment were the marked inhibition of pMAPK and up-regulation of p57, just like the influence of MEK inhibitor, U0126. Progesterone also induced growth inhibition and a slight accumulation of cells in the G1 phase of the cell cycle. On the other hand, the effects of progesterone were diminished in the presence of its antagonist mifepristone (RU-486). Taken together, these results suggest that progesterone treatment may induce the expression of the p57 on the mRNA and protein level by the progesterone receptor and that the MAPK signaling pathway may be involved in the progesterone-induced antiproliferative effect.
摘要-----------------------------------------------------------------------------1
Abstract--------------------------------------------------------------------------2
緒論-----------------------------------------------------------------------------4
一、前言-----------------------------------------------------------------4
二、細胞週期(Cell Cycle)--------------------------------------------5
三、細胞週期調節基因p57------------------------------------------6
四、MAPK訊息傳遞途徑--------------------------------------------8
五、Progesterone--------------------------------------------------------9
六、鼻咽癌(Nasopharyngeal carcinoma)---------------------------11
實驗材料與方法--------------------------------------------------------------14
結果與討論--------------------------------------------------------------------24
結論-----------------------------------------------------------------------------29
參考文獻-----------------------------------------------------------------------30
附圖-----------------------------------------------------------------------------42
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