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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 廖憶純(Yi-Chun Liao) | |
| dc.contributor.author | Yi-Chou Liu | en |
| dc.contributor.author | 劉益洲 | zh_TW |
| dc.date.accessioned | 2021-06-15T13:56:41Z | - |
| dc.date.available | 2020-08-26 | |
| dc.date.copyright | 2015-08-26 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-25 | |
| dc.identifier.citation | 張佳鈞 (2013) 表皮生長因子促進 CTEN 基因表現之機制探討，張佳鈞主編，國立台灣大學生命科學院生化科技學系
楊寬 (2014) 前列腺細胞中 ΔNp63調控CTEN 基因進而參與細胞貼附與遷移機制，楊寬主編，國立台灣大學生命科學院生化科技學系 Ahearn, I. M., Haigis, K., Bar-Sagi, D., & Philips, M. R. (2012). Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol, 13(1), 39-51. Al-Ghamdi, S., Cachat, J., Albasri, A., Ahmed, M., Jackson, D., Zaitoun, A., Ilyas, M. (2013). C-terminal tensin-like gene functions as an oncogene and promotes cell motility in pancreatic cancer. Pancreas, 42(1), 135-140. Albasri, A., Seth, R., Jackson, D., Benhasouna, A., Crook, S., Nateri, A. S., Ilyas, M. (2009). C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer. J Pathol, 218(1), 57-65. Auger, K. R., Songyang, Z., Lo, S. H., Roberts, T. M., & Chen, L. B. (1996). Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes. J Biol Chem, 271(38), 23452-23457. Burridge, K., Fath, K., Kelly, T., Nuckolls, G., & Turner, C. (1988). 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The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res Int, 2013, 546318. Schultz, D. J., Wickramasinghe, N. S., Ivanova, M. M., Isaacs, S. M., Dougherty, S. M., Imbert-Fernandez, Y., . . . Klinge, C. M. (2010). Anacardic acid inhibits estrogen receptor alpha-DNA binding and reduces target gene transcription and breast cancer cell proliferation. Mol Cancer Ther, 9(3), 594-605. Shikama, N., Lee, C. W., France, S., Delavaine, L., Lyon, J., Krstic-Demonacos, M., & La Thangue, N. B. (1999). A novel cofactor for p300 that regulates the p53 response. Mol Cell, 4(3), 365-376. Stein, R. W., Corrigan, M., Yaciuk, P., Whelan, J., & Moran, E. (1990). Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity. J Virol, 64(9), 4421-4427. Sung, B., Pandey, M. K., Ahn, K. S., Yi, T., Chaturvedi, M. M., Liu, M., & Aggarwal, B. B. 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(2000). Phosphorylation of p300 at serine 89 by protein kinase C. J Biol Chem, 275(52), 40946-40951. Yuan, L. W., Soh, J. W., & Weinstein, I. B. (2002). Inhibition of histone acetyltransferase function of p300 by PKCdelta. Biochim Biophys Acta, 1592(2), 205-211. Zaidel-Bar, R., & Geiger, B. (2010). The switchable integrin adhesome. J Cell Sci, 123(Pt 9), 1385-1388. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51908 | - |
| dc.description.abstract | EGFR signaling 是細胞複雜的訊息傳遞途徑之一，而 EGFR 的訊息可透過調控 tensin 家族的 tensin3 及 CTEN 蛋白質含量的消長，使蛋白質含量增加的 CTEN 取代 tensin3，進而拆卸肌動蛋白絲，增強乳癌細胞遷移的能力，但 EGFR 訊息傳導調控 CTEN 表現量上升機制目前仍不清楚。本論文的研究發現，在人類正常前列腺細胞株 RWPE-1 以及人類子宮頸癌細胞株 HeLa 中，若 knockdown p300 時會降低 EGF 誘導 CTEN 之 mRNA 表現量以及蛋白質含量，證實 p300 確實參與了 EGF signaing 調控 CTEN 的途徑。我們進一步證明了 HeLa 細胞受到 EGF 刺激後，透過 MEK/ERK 的訊息傳遞可使 p300 結合上 CTEN 啟動子，並增加 CTEN 啟動子上 histone acetylation 的修飾，以活化 CTEN 基因表現。EGF 也可透過 MEK/ERK pathway 來誘導 HeLa 細胞中 p300 的磷酸化，因此我們推測 EGF signaling 是經由 MEK/ERK 的訊息傳遞促使 p300 磷酸化，進而提升其histone acetyltransferase 的活性，並與 CTEN 啟動子結合而促進 CTEN 基因表現。 | zh_TW |
| dc.description.abstract | Epidermal growth factor receptor (EGFR) signaling is one of the complex signal transduction pathways. Following EGF stimulation, tensin3 expression is downregulated and CTEN is upregulated, to a level that is sufficient for displacement of tensin3 from integrin. Then tensin3 dissociates from focal adhesion, leading to the breakdown of F-actin and initiation of cell migration in breast cancer. However, the mechanism of EGFR-induced CTEN gene expression is still unclear. Our results have shown that knockdown p300 expression could decrease EGF-induced CTEN mRNA and protein levels in a normal human prostate cell lines, RWPE-1, and a human cervical cancer cell line, HeLa. It indicates that p300 participates in the EGF-regulated CTEN expression. We further demonstrate that after EGF stimulation, p300 is recruited to CTEN promoter through MEK/ERK pathway in HeLa cells, and increases histone acetylation on CTEN promoter to activate CTEN gene expression. EGF also induces the phosphorylation of p300 through MEK/ERK pathway in HeLa cells. Therefore, our study suggests that EGF signaling induces the phosphorylation of p300 through MEK/ERK pathway, thereby enhancing its histone acetyltransferase activity, and in turn recruits an increased level of p300 to CTEN promoter to activate CTEN gene expression. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T13:56:41Z (GMT). No. of bitstreams: 1 ntu-104-R02b22034-1.pdf: 1208176 bytes, checksum: f9c5e0129471d0520ff973656567d69b (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 目錄 i
縮寫表 iii 摘要 v Abstract vi 1. 本論文之研究基礎 1 1.1 表皮生長因子受體之訊息傳導路徑 1 1.2 Focal adhesion 2 1.3 CTEN 3 1.4 CTEN 受到 EGF siganling pathway 調控之機制 5 1.5 p300 6 1.6 本論文之研究目的 8 2. 材料與方法 9 2.1 實驗材料 9 2.1.1 菌種 9 2.1.2 質體 DNA 9 2.1.3 細胞株 10 2.1.4 細胞培養基 10 2.2 實驗方法 10 2.2.1 細胞相關實驗 10 2.2.2 DNA 分析及質體建構 13 2.2.3 RNA 分析 15 2.2.4 蛋白質分析 16 2.2.5 染色質免疫沉澱 (Chromatin Immunopreciptation, ChIP) 17 3. 研究結果 20 3.1 p300 參與 EGF 對 CTEN 基因表現的調控 20 3.2 EGF 經由 MEK/ERK pathway 調控 CTEN 啟動子上 histone 的 acetylation 21 3.3 EGF 透過 MEK/ERK pathway 促進 p300 與 CTEN 啟動子區域的結合 22 3.4 EGF signaling 透過 p300 影響 CTEN 啟動子區域 histone acetylation 23 3.5 EGF 對 p300 磷酸化之影響 23 4. 討論與未來研究方向 25 5. 參考文獻 30 6. 圖與表 35 | |
| dc.language.iso | zh-TW | |
| dc.subject | 轉錄因子 | zh_TW |
| dc.subject | 表皮生長因子 | zh_TW |
| dc.subject | EGF | en |
| dc.subject | CTEN | en |
| dc.subject | histone modification | en |
| dc.subject | Tensin | en |
| dc.subject | focal adhesion | en |
| dc.subject | p300 | en |
| dc.title | p300 參與表皮生長因子促進 CTEN 基因表現之調控機制 | zh_TW |
| dc.title | p300 Is Involved in the Regulatory Mechanism of EGF-induced CTEN Gene Expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 謝淑貞(Shu-Chen Hsieh),黃楓婷(Feng-Ting Huang),賴韻如(Yun-Ju Lai) | |
| dc.subject.keyword | 表皮生長因子,轉錄因子, | zh_TW |
| dc.subject.keyword | p300,focal adhesion,CTEN,EGF,Tensin,histone modification, | en |
| dc.relation.page | 48 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-25 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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