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研究生:高大朋
研究生(外文):Ta-Peng Kao
論文名稱:在三陰性乳腺癌中調節MZF-1B誘發IGF-1R與ERα之表現
論文名稱(外文):Modulation of MZF-1B induces the expression of IGF-1R and ERα in triple-negative breast cancer cells
指導教授:黃俊銘黃俊銘引用關係
指導教授(外文):Jin-Ming Hwang
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:應用化學系碩士班
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:51
中文關鍵詞:三陰性乳腺癌
外文關鍵詞:TNBCMZF-1BIGF-1RERα
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  三陰性乳腺癌 (TNBC) 由於缺乏雌激素受體(ER)、黃體素受體 (PR) 與第二型人類表皮生長因子受體 2 (HER-2) 表達,被認為是乳腺癌表型中最難治療之類型。近十年來研究重點在於找尋治療靶點,如將 TNBC 細胞逆轉成 ER陽性乳癌細胞。
  本研究透過利用 shRNA MZF-160-72 抑制 MZF-1B 會增進 IGF-1R 與ERα 之表達。IGF-1R可透過 p38 MAPK signaling pathway 控制 ERα 之表達,而IGF-1R則是受到 MZF-1B在轉錄階段下之直接調控。然而在抗癌藥物 (Cisplatin、Tamoxifen citrate 與 Letrozole)敏感性之實驗結果發現,經抑制 MZF-1B 之 TNBC 細胞與原始TNBC細胞之間之抗癌藥物敏感性並無顯著差異。因此未來若可克服抗癌藥物敏感性實驗結果之問題,此些發現可為 TNBC 之治療提供新的策略方向。
  Triple-negative breast cancer (TNBC) is considered as the most difficult therapeutic phenotypes of breast cancer due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expressions. Over the last decade, the current focus of treatment research is hunting for therapeutic targets, as TNBC cells reversal to ER-positive breast cancer cells.
  This research discover that when down-regulated MZF-1B by shRNA MZF-160-72 transfection, the IGF-1R and ERα expression were increased. The expression of ERα was controlled by IGF-1R through p38 MAPK signaling pathway, while IGF-1R was regulated directly by MZF-1B in a transcriptional level. Whereas, the anti-cancer drugs (cisplatin, tamoxifen citrate and letrozole) sensitivity test showed that there were not significant difference in the MZF-1B-down-regulated-and original- TNBC cells. Therefore, if the result of anti-cancer drugs sensitivity can be overcome in the future, these findings will provide a new strategy for TNBC therapy.
致謝 --------------------------------------------------------------------------------------------- 1
中文摘要 --------------------------------------------------------------------------------------- 3
英文摘要 --------------------------------------------------------------------------------------- 4
緒論
  一、癌症 (Cancer)
    1-1 影響程度 ---------------------------------------------------------------------- 5
    1-2 形成過程與特性 ------------------------------------------------------------- 6
  二、乳癌 (Breast Cancer)
    2-1 影響程度 ---------------------------------------------------------------------- 8
    2-2 乳癌分期與種類 ------------------------------------------------------------- 9
    2-3 三陰性乳腺癌 -------------------------------------------------------------- 10
    2-4 治療乳腺癌之藥物 -------------------------------------------------------- 11
  三、生長因子
    3-1 MZF-1 ------------------------------------------------------------------------- 12
    3-2 IGF-1 -------------------------------------------------------------------------- 12
    3-3 ER ------------------------------------------------------------------------------ 13
研究動機 -------------------------------------------------------------------------------------- 14
實驗材料與器材 ----------------------------------------------------------------------------- 16
實驗方法
  1. 細胞培養 (Cell Culture) ---------------------------------------------------------- 18
  2. 細胞存活率實驗 (Cell Viability assay) ─ MTT assay ----------------------- 20
  3. 西方墨點法 (Western Blot) ------------------------------------------------------ 21
實驗結果 -------------------------------------------------------------------------------------- 23
研究討論 -------------------------------------------------------------------------------------- 26
文獻 -------------------------------------------------------------------------------------------- 28
圖表與說明 ----------------------------------------------------------------------------------- 32
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