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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林欽塘(Chin-Tarng Lin) | |
| dc.contributor.author | Yuan-Sung Kuo | en |
| dc.contributor.author | 郭源松 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:19:26Z | - |
| dc.date.available | 2011-07-01 | |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-20 | |
| dc.identifier.citation | Adamson ED, Mercola D: Egr1 Transcription Factor: Multiple Roles in Prostate
Tumour Cell Growth and Survival. Tumor Biol 2002; 23:93-102 Bach LA, Hsieh S, Sakano K, et al. Bindings of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6. J Biol Chem 1993; 268:9246-9254 Bach LA. IGFBP-6 five years on; not soforgotten? Growth Hormone & IGF Research 2005; 15:185–192 Baek SJ, Kim JS, Moore SM, Lee SH, Martinez J, Eling TE. Cyclooxygenase inhibitors induce the expression of the tumour suppressor gene EGR-1, which results in the up-regulation of NAG-1, an antitumorigenic protein. Mol Pharmacol 2005; 67:356-364 Bargou RC, Wagener C, Bommert K, Arnold W, Daniel PT, Mapara MY et al. Blocking of Transcription Factor E2F/DP by Dominant-Negative Mutants in a Normal Breast Epithelial Cell Line Efliciendy Inhibits Apoptosis and Induces Tumor Growth in SCID Mice. J Exp Med 1996; 183: 1205-121 Baron V, Adamson ED, Calogero A, Ragona G, Mercola D. The transcription factor Egr-1 is a direct regulator of multiple tumor suppressors including TGFβ-1, PTEN, p53 and fibronectin. Egr1 is a potential target of gene therapy for prostate cancer. Cancer Gene Ther 2006; 13(2): 115-124 CalogeroA, Lombari V, De Gregorio G, Porcellini A, Ucci S, Arcella S, et al. Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma. Cancer Cell International 2004; 4:1 Chow LS, Lam CW, Chan SY, Tsao SW, To KF, Tong SF, et al. Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. Oncogen 2006; 25:310-316 Department of Health, Executive Yuan R.O.C. (Taiwan), 2007 Firth SM, Baxter RC: Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 2002;23:824-854 Gallicchio MA; Kneen M; Hall C; Scott AM; Bach LA. Overexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growth in vivo. Int J Cancer 2001; 94:645-657 Grellier P, Berrebi D, and Bsbajko S. 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Effect of Epstein-Barr virus infection on global gene expression in nasopharyngeal carcinoma. Funct Integr Genomics 2007; 7:79-93 Leng SL, Leeding KS, Whitehead RH, and Bach LA. Insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced but not basal proliferation and adhesion of LIM 1215 colon cancer cells. Molecular and Cellular Endocrinology 2001; 174:121-127 Lin CT, Chan WY, Chen W, Huang HM, Wu HC, Hsu MM, et al. Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest 1993; 68:716-727 Lin CT, Lin CR, Tan GK, Chen W, Dee AN, Chan WY. The mechanism of Epstein-Barr Virus Infection in Nasopharyngeal Carcinoma Cells. Am J Pathol 1997; 150:1745-1756 Lin CT, Wong CI, Chan WY, Tzung KW, Ho JK, Hsu MM, et al.. Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest 1990; 62:713-724 Lin CT. 2006 Epstein-Barr virus: new research in epithelial carcinoma. In New Developments in EBV Research, Ulmar CS (ed.). Nova Science: New York, 2004:71-91 Liu C, Adamson E, Mercola D. Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1. Proc Natl Acad Sci U S A 1996; 15; 93(21): 11831–11836 Liu C, Calogero A, Ragona G, Adamson E, Mercola D. EGR-1, the reluctant suppression factor: EGR-1 is known to function in the regulation of growth, differentiation, and also has significant tumor suppressor activity and a mechanism involving the induction of TGF-beta1 is postulated to account for this suppressor activity. Crit Rev Oncog 1996; 7(1-2): 101-25 Liu C, Rangnekar VM, Adamson E, Mercola D. Suppression of growth and transformation and induction of apoptosis by EGR-1. Cancer Gene Ther 1998; 5(1): 3-28 Martin JL, Willetts KE, Baxter RC. Purification and properties of a novel insulin-like growth factor-II binding protein from transformed human fibroblasts. J Biol Chem1990; 265:4124-4130 Niedobitek G, Young LS, Sam CK, Brooks L, Prasad U, Rickinson AB. Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferential nasopharyngeal carcinoma. Am J Pathol 1992; 140:879-887 Oh Y, Nagalla SR, Yamanaka Y. Synthesis and characterization of insulin-like growth factor binding protein-7 (IGFBP-7). J Biol Chem 1996; 271:30322–30325 Pascale Grellier, Brigitte De Galle, Sylvie Babajko. Expression of insulin-like growth factor-binding protein 6 complementary DNA alters neuroblastoma cell growth. Cancer Research 1998; 58:1670-1676 Plymate SR, Tennant M, Bringaum RS, Thrasher JB, Chatta G, Ware JL. The effect on the insulin-like growth factor system in human prostate epithelial cells of immortalization and transformation by simian virus-40 T antigen. J Clin Endocrinol Metab 1996; 81:3709-3716 Shanmugaratnam K. Histological Typing of Tumours of the Upper Respiratory Tract and Ear, 2ndedn. 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Int J Cancer 1982; 29:139-141 Zeng ZY, Zhou YH, Zhang WL, Xiong W, Fan SQ, Li XL, et al. Gene expression profiling of nasopharyngeal carcinoma reveals the abnomally regulated Wnt signaling pathway. Hum pathol 2007; 38:120-133 zur Hausen H, Schulte-Holthausen H, Klein G, Henle W, Henle G, Clifford P, et al. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 1970; 228:1056-8 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46624 | - |
| dc.description.abstract | 鼻咽癌在東南亞頗為盛行，尤其是中國南方、新加坡及台灣。本研究的目的是藉由實驗發現鼻咽癌進行時關鍵基因的變化。之前我們以利用 microarray 比較鼻咽癌和正常鼻黏膜細胞篩選出 18 種基因，再經由 Q-RT-PCR 和組織免疫染色發現 IGFBP-6 在鼻咽癌細胞的表現和正常鼻黏膜細胞比較有顯著的減少。為探討 IGFBP-6 在鼻咽癌腫瘤生長時的作用，我們建立 IGFBP-6 轉染的鼻咽癌穩定並可被 Doxycycline 調控 IGFBP-6 表現的細胞株，進行試管及活體功能性分析，發現 IGFBP-6 表現增加時鼻咽癌細胞的增生、侵犯及轉移能力均顯著降低且讓細胞凋亡數目明顯增加；進一步分析發現 EGR-1、 Caspase-1及 TSP-1 等基因表現也明顯降低。利用 siRNA 抑制 EGR-1 的基因表現，Caspase-1及 TSP-1 表現也降低，但 IGFBP-6 的表現及鼻咽癌細胞的移動能力則不受影響。 Chromatin immunoprecipitation 和 luciferase reporter 實驗證明 IGFBP-6 能黏結在 EGR-1的 promoter 上並啟動 EGR-1 基因表現。總結來說， IGFBP-6 能經由調控 EGR-1 的表現來影響鼻咽癌的進行，因此， IGFBP-6 可能被利用來作為治療鼻咽癌的標的。 | zh_TW |
| dc.description.abstract | Nasopharyngeal carcinoma (NPC) is prevalent in southeastern Asia, particularly southern China, Singapore and Taiwan. The aim of this study was to identify the pivotal genes that may be altered during NPC progression. Using cDNA microarray analysis, we compared the expression of 18 genes between NPC and normal nasomucosal cells. Q-RT-PCR analysis found the expression of IBFBP-6 in NPC cell lines and immunolocalization of IGFBP-6 in NPC to be very weak. To explore the effects of IGFBP-6 on NPC tumour growth, we constructed inducible plasmids containing full length of IGFBP-6 c-DNA (pBIG2i-IGFBP-6) and established pBIG2i-IGFBP-6 transfected NPC stable cell lines (NPC-TW01-pBIG2i-IGFBP-6). We then performed functional analysis of the IGFBP-6 in cell lines in vitro and in vivo. Overexpression of IGFBP-6 significantly suppressed the proliferation, invasion, and metastatic activity of NPC cells and increased their apoptosis. We found EGR-1, caspase-1 and TSP-1 genes to be markedly upregulated when NPC-pBIG2i-IGFBP-6 was treated with doxycycline. Knocking down EGR-1 with EGR-1 siRNA resulted in a decrease in expression of caspase-1, TSP-1 and EGR-1, but not the expression of IGFBP-6. However, in knockdown cells the unchanged expression of IGFBP-6 did not inhibit the migration of NPC cells. Chromatin immunoprecipitation and luciferase reporter assay experiments showed that IGFBP-6 bound the EGR-1 promoter regions and activated EGR-1 promoter. We conclude that IGFBP-6 can regulate the progression of NPC by regulating the expression of EGR-1. These results suggest that IGFBP-6 could be used as a new target in NPC therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:19:26Z (GMT). No. of bitstreams: 1 ntu-99-D88444002-1.pdf: 1579403 bytes, checksum: 4e013fd7fc4f38f352a895229b8c0c64 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 中文摘要･････････････････････････････････ ････1
Abstract･････････････････････････････････ ････2 Introduction･･････････････････････････････ ･･･3 Materials & Methods･･････････････････････････ 6 Results･････････････････････････････････････ 19 Discussion･･･････････････････････････････････24 References･･･････････････････････････････････27 Tables･･････････････････････････････････････ 33 Figures･････････････････････････････････････ 37 | |
| dc.language.iso | en | |
| dc.subject | IGFBP-6 | zh_TW |
| dc.subject | 鼻咽癌 | zh_TW |
| dc.subject | EGR-1 | zh_TW |
| dc.subject | 鼻咽癌進行 | zh_TW |
| dc.subject | IGFBP-6 | en |
| dc.subject | Nasopharyngeal carcinoma (NPC) | en |
| dc.subject | NPC progression | en |
| dc.subject | EGR-1 | en |
| dc.title | IGFBP-6經由調控EGR-1的表現在鼻咽癌細胞中扮演抑癌基因的角色 | zh_TW |
| dc.title | IGFBP-6 plays a role as an oncosuppressor gene in NPC pathogenesis through regulating EGR-1 expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 吳漢忠(Han-Chung Wu) | |
| dc.contributor.oralexamcommittee | 李德章(Te-Chang Lee),陳瑞華(Ruey-Hwa Chen),蘇燦隆(Tsann-Long Su),洪瑞隆(Ruey-Lomg Hong),林中梧(Chung-Wu Lin),李明學(Ming-Shyue Lee) | |
| dc.subject.keyword | 鼻咽癌,鼻咽癌進行,IGFBP-6,EGR-1, | zh_TW |
| dc.subject.keyword | Nasopharyngeal carcinoma (NPC),NPC progression,IGFBP-6,EGR-1, | en |
| dc.relation.page | 46 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-21 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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