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研究生:賴麗娟
研究生(外文):Li-Chuan Lai
論文名稱:在神經膠質瘤細胞抑制Pin1的表現會加強對放射線的敏感性
論文名稱(外文):Inhibition of Pin1 expression enhances radiosenstivity in glioma cells
指導教授:陳一村
指導教授(外文):I-Tsuen Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學生物技術暨檢驗學系暨研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:54
中文關鍵詞:放射線神經膠質瘤細胞
外文關鍵詞:Pin1radiosenstivityglioma
相關次數:
  • 被引用被引用:2
  • 點閱點閱:139
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  • 下載下載:11
  • 收藏至我的研究室書目清單書目收藏:0
Pin1 為 PPIase (peptidyl-prolyl isomerase) 家族的異構�﹛A可以特異性的辨認某些蛋白被磷酸化的 Ser/Thr-Pro motifs。Pin1 會調節蛋白並造成構形改變,進而去影響蛋白功能。許多參與細胞週期調控、DNA 損傷反應、轉錄調節和神經生長的蛋白,都會被 Pin1 辨認而影響。Pin1 過量表現也常伴隨著 β-catenin 和 cyclin D1 的上升。在許多人類癌症都可以發現 Pin1 大量表現,所以認為 Pin1會促進腫瘤生成。先前的實驗,我們發現對放射線有抗性的神經膠質瘤細胞,Pin1的表現量會增加,所以我們提出了假說,在神經膠質瘤細胞將 Pin1 knockdown或許會增加細胞對放射線的敏感性。實驗結果顯示,在 GBM8401 和 GBM8401-R2 細胞將 Pin1 knockdown,會降低細胞對放射線和抗癌藥TMZ的抵抗性,而減少細胞存活率和細胞群落生成能力。除此之外,降低 Pin1 表現量也會伴隨著 cyclin D1 和 E2F1 的減少。這些結果也可在 CD133 positive GBM 細胞 (S1 and S1R1,Pin1 表現過量) 看到。相反的,外加入 Pin1 至 GBM8401 細胞會增加細胞對放射線的抗性,而增加細胞存活率和細胞群落生成能力。由我們的結果建議,在神經膠質瘤細胞抑制 Pin1 的表現會加強對放射線的敏感性。
The Pin1 gene was first identified in a genetic screen for proteins involved in mitotic regulation. Pin1, a peptidyl-prolyl isomerase, is a highly conserved enzyme that isomerizes only the pSer/Thr-Pro motifs in certain proteins, thereby inducing conformational changes. Several phosphoproteins involved in cell cycle control, DNA damage responses, transcriptional regulation and neuronal survival, are recognized and affected by Pin1. Pin1 over-expression is often associated with up-regulation of β-catenin and cyclin D1. Pin1 has been shown to be overexpressed in many human cancers, suggesting its role in tumor development. Previously, we found that enhanced Pin1 expression in glioma cells correlated with their radiation resistance. This has prompted us to test the hypothesis that Pin1 knockdown could sensitize glioma cells to radiation. Here we report that Pin1 knockdown reduced cell viability and clonogenic survival in response to radiation or chemodrug (TMZ) in GBM8401 and radiation-resistant GBM8401-R2 cells. In addition, cyclin D1 or E2F1 reduction correlated with decreased Pin1 expression. These findings are also shown in CD133 positive GBM cells (S1 and S1R1) which overexpress Pin1. In contrast, ectopic expression of Pin1 in GBM8401 cells increased cell viability and clonogenic survival in response to radiation treatment. Our results suggest that Inhibition of Pin1 expression causes radiosenstization in glioma cells.
中文摘要………………………………………………………2
英文摘要………………………………………………………3
一、緒論………………………………………………………4
二、材料與實驗方法…………………………………………11
三、實驗結果…………………………………………………23
四、實驗討論…………………………………………………28
五、參考文獻…………………………………………………31
六、圖表………………………………………………………38
七、supplementary…………………………………………...47
八、附錄………………………………………………………48
五、參考文獻
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60. 羅智文。具放射線抗性之腦腫瘤細胞的特徵與Pin1在其中所參與的角色。
2008陽明大學醫學生物技術暨檢驗學系暨研究所碩士論文。

61. 許登發。在卵巢癌細胞中穩定表現PIN1並探討其對細胞死亡的影響。
2008陽明大學醫學生物技術暨檢驗學系暨研究所碩士論文。
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