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研究生:陳虹諺
研究生(外文):Hung-Yen Chen
論文名稱:探討人類第三型POU結構域二號因子基因在人類胃癌發展進程中之角色
論文名稱(外文):Study of the human POU3F2 gene mediated aggressive phenotypes in human gastric cancer cells
指導教授:林宜玫林宜玫引用關係
指導教授(外文):Yi-Mei J. Lin
口試委員:闕斌如楊肇基
口試日期:2016-07-25
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生物醫學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:48
中文關鍵詞:人類第三型POU結構域二號因子胃癌增生侵襲轉移
外文關鍵詞:POU3F2gastric cancerproliferationInvasionMigration
相關次數:
  • 被引用被引用:0
  • 點閱點閱:140
  • 評分評分:
  • 下載下載:7
  • 收藏至我的研究室書目清單書目收藏:0
癌症一直都是十大死亡原因的第一位,其中胃癌居第七位。對於早期胃癌完全切除是唯一的方式,但手術只單純提供晚期的患者20%生存率。目前相關於胃癌的機制尚未清楚,藉由本次研究有助於更加了解胃癌的機制。POU3F2是在神經細胞和黑色素瘤細胞中表達的一個POU-同源域轉錄因子。該POU3F2基因已經在幾個黑色素瘤細胞株中發現,但不在黑色素細胞中,並且證據顯示黑素細胞瘤的成長通過促進細胞增殖,轉移和侵襲使,而抑制POU3F2表達顯示出了相反的結果。然而,POU3F2在胃癌中的作用還沒有被調查。
在這項研究中我們試圖澄清POU3F2在胃癌中的作用。我們透過直接細胞計數、細胞倍增時間(螢光)和xCELLigence系統(電阻)細胞增生實驗發現了POU3F2促進胃腺癌AGS細胞的增生,而且我們在不同表現量的穩定純系(Stable clone)細胞也觀察到正相關,同時我們也以西方墨點法確認POU3F2促進磷酸化Akt和磷酸化ERK的表現。此外我們使用轉染將AGS胃癌細胞株過度表現POU3F2藉由轉孔法證實會促進侵襲與轉移能力。我們將進一步了解POU3F2在胃癌進展等多重作用,並通過使用慢病毒感染shPOU3F2敲除POU3F2觀察其對胃癌的作用。我們敲除POU3F2藉由西方墨點法、細胞計數及轉孔法得到了相反的結果,再次證實了POU3F2的表現與細胞增生、侵襲及轉移的關係。


Cancer has been ranked as the first leading cause of death, and gastric cancer is the seventh most common cause of cancer-related death in Taiwan. Although complete surgical resection remains the only curative modality for early stage gastric cancer, surgery alone only provides long-term survival in 20% of patients with advanced-stage disease. The mechanism in gastric cancer is still unclear. Our study helps us to understand more about the mechanisms of gastric cancer. POU3F2 is a POU-Homeodomain transcription factor, and has been proved to play a critical role in melanoma growth via promote cell proliferation. The POU3F2 gene has been found in several melanoma cell lines, but not in melanocytes, and evidences implicate its role in melanoma growth via promote cell proliferation, migration and invasion, while inhibits POU3F2 expression shown opposite results. However, the role of POU3F2 in gastric cancer has not been investigated.
In this study, we attempted to clarify the role of POU3F2 in gastric cancer. We found the POU3F2 also promote gastric adenocarcinoma AGS cell proliferation by direct cell counting ,cell doubling time (fluorometric) and xCELLigence System (electrical impedance) cell viability assay, and we also observed that POU3F2 promote level of phosphorylated Akt and phosphorylated ERK. Moreover, overexpression POU3F2 also promote invasion and migration by transwell assay in AGS cell. We will further elucidating the multiple role of POU3F2 in gastric cancer progression, and to observe the effects on gastric cancer by using shPOU3F2 to knowdown POU3F2.


中文摘要 i
Abstract ii
目次 iii
圖次目 vi
前言 1
胃癌 1
有絲分裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)路徑 1
PI3K/AKT/mTOR路徑 2
POU結構域家族與DNA的結合(POU domain family and DNA binding) 3
POU3F2 基因結構與介紹 4
POU3F2對神經發育(Neural development)的影響 5
POU3F2在黑色素細胞瘤中的各種影響 5
對細胞增生的影響 5
對細胞週期(cell cycle)的影響 6
對上皮間質轉變(Epithelial-mesenchymal transitions, EMT)的影響 6
POU3F2在其他癌症細胞中的角色 7
POU3F2 對於腎癌細胞中扮演的角色 7
POU3F2 對於神經膠質瘤(glioblastoma)細胞中扮演的角色 7
研究目的 8
材料 9
胃癌細胞株(Gastric Cancer cell line) 9
RPMI 培養基(medium) 9
RIPA 裂解緩衝溶液(lysis buffer) 9
五倍蛋白質樣品(protein sample)緩衝溶液 9
iv
Tris 緩衝溶液 10
10% 過硫酸銨(ammonium persulfate, APS)溶液 10
跑膠(Running)緩衝溶液 10
轉印(Transfer)緩衝溶液 10
麗春紅(Ponceau S)溶液 10
Tris-Buffered Saline Tween 20
(TBST)緩衝溶液 10
封閉(Blocking)緩衝溶液 10
一級抗體(Primary Antibody) 11
二級抗體(Secondary antibody) 11
Luria-Bertani(LB)液態培養基 11
POU3F2 質體( plasmid) 11
方法 12
細胞培養 12
蛋白質萃取 12
蛋白質定量分析 12
西方墨點法(Western Blot) 13
質體(plasmid)萃取 14
轉染(Transfection) 14
穩定純系(Stable clone)細胞 14
細胞計數(cell counting) 15
即時電阻測量系統(xCELLigence RTCA Systems) 15
細胞倍增時間(Cell Doubling-Time) 15
侵襲實驗(Invasion assay) 16
轉移實驗(Migration assay) 16
shRNA 敲除(knockdown) 17
v
統計方法 17
實驗結果 18
不同惡性程度的胃癌細胞中 POU3F2 的表現 18
過量表現 POU3F2 增加細胞的增生 18
過量表現 POU3F2 對於細胞週期的影響 19
過量表現 POU3F2 促進磷酸化Akt 與ERK 19
過量表現 POU3F2 增加細胞轉移與侵襲的能力 20
敲除 POU3F2 減少細胞增生以及轉移與侵襲的能力 20
討論 21
POU3F2 表現程度與增生的探討 21
POU3F2 對於細胞週期探討 21
POU3F2 對於PI3K/Akt 和ERK/MAPK路徑活化與後續實驗探討 22
POU3F2 對於侵襲與轉移能力探討 22
敲除 POU3F2 對於胃癌細胞影響之探討 22
POU3F2 對於Notch 訊號路徑 23
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