成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	盧珮珊 Lu, Pei-Shan
論文名稱：	探討Nucleolin在肺癌形成中的轉錄機制 To dissect the transcriptional mechanism of nucleolin in lung cancer tumorigenesis
指導教授：	洪建中 Hung, Jan-Jong
學位類別：	碩士 Master
系所名稱：	生物科學與科技學院 - 生物資訊與訊息傳遞研究所 Insitute of Bioinformatics and Biosignal Transduction
論文出版年：	2012
畢業學年度：	100
語文別：	中文
論文頁數：	83
中文關鍵詞：	Nucleolin 、Sp1 、EGFR 、Kras 、肺癌
外文關鍵詞：	Nucleolin, Sp1, EGFR, Kras, Lung cancer
相關次數：	點閱：75 下載：1
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

肺癌為十大癌症之一，在世界衛生組織的統計之下，每年約有 140 萬人死於肺癌。而且合併計算其它併發症的病人，肺癌的五年存活率只有 15.2%，相較低於其他癌症。 Nucleolin在細胞具有許多的功能，包含了調控細胞增生、細胞凋亡、mRNA 的穩定性等。先前的研究已經指出 nucleolin 會在腫瘤細胞中大量表現，然而其分子機轉仍然不清楚。在先前實驗室建立的Kras 誘導肺癌轉殖鼠看到隨著四環黴素(Doxycyclin) 的餵食會有腫瘤形成的現象。在這些肺癌腫瘤中我們去分析nucleolin mRNA的表現量，的確隨著四環黴素的餵食時間增加而增加。這樣的結果，讓我們懷疑在肺癌癌化過程中，Kras路徑對於nucleolin的累積是否扮演重要的腳色。非小細胞肺癌的病患中常常可以偵測到基因的突變，約三到五成為腺癌(adenocarcinoma)的類型，其中Kras突變好發於西方人，EGFR突變則好發於東方人。實驗室先前的研究也指出，隨著四環黴素的餵食Kras誘導肺癌轉殖鼠，specific protein 1 (Sp1) 同樣也會高度表現。在肺癌癌化過程中，Sp1高度表現和nucleoiln的累積是否有關連性目前仍然未知。首先，我們利用FTI-276 (Kras抑制劑) 去處理細胞,發現nucleolin的轉錄活性(transcriptional activity) 會被抑制。之後我們利用EGF去處理細胞發現會使nucleolin的蛋白質表現、mRNA 和轉錄活性都上升；反之處理Gefinitib (EGFR 抑制劑) 則會抑制nucleolin的轉錄活性。此結果顯示Kras 及EGFR調控路徑有可能在肺癌形成中對nucleolin的累積有重要的影響。為了深入了解nucleolin 在肺癌形成中的轉錄機制，我們分析了nucleolin的啟動子(promoter)，發現有5個 Sp1結合位置在 nucleolin啟動子上。而這些Sp1 結合位置的刪除會明顯地降低 nucleolin的轉錄活性。此外，過度表現Sp1會增加nucleolin表現量; 反之抑制Sp1，nucleolin則會降低。最後，實驗室建立的EGFR (exon19 deletion) 誘導肺癌轉殖鼠在肺癌形成中，nucleolin會大量表現。綜合以上實驗我們得知Sp1可能會透過Kras及EGFR的路徑參與在nucleolin的上升中，這些結果可以讓我們更加了解肺癌形成的機制及nucleolin在其中扮演的角色，而且進一步有助肺癌的研究及治療。

Lung cancer is the most common cause of death in both men and women throughout the world. Survival rates for lung cancer are generally lower than those for most cancers, with an overall five-year survival rate for lung cancer of about 15.2% compared to other cancer for example 64.4% for colon cancer. Previous studies reveal that nucleolin is a multifunctional protein involved in RNA stability, apoptosis and so on. In the past cancer research, nucleolin was found to be accumulated in tumerigenesis. However, the transcriptional mechanism remains unclear. Our preliminary data found that nucleolin was also accumulated in Kras-induced lung cancer transgenic mice, implying that Kras-pathway might be related to nucleolin accumulation. In western countries, the Kras mutation rate is high in patients with NSCLC, especially in those with adenocarcinoma (30%-50%), but high EGFR mutation rates in East Asia. In addition, our previous study indicated that specific protein 1 (Sp1) level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Whether the nucleoiln accumulation in lung tumorigenesis is associated with highly expressed Sp1 in lung cancer is still unknown. Here, inhibition of Kras activity by inhibitor, FTI-276, declined the transcriptional activity of nucleolin. In addition, we also used EGF or Epithelial Growth Factor Receptor (EGFR) inhibitor, Gefitinib, to treat cell, and found that nucleolin could be activated or repressed in its protein level, mRNA level and transcriptional activity, respectively. These results figure out EGFR- and Kras- pathways induced in lung cancer formation might be important for nucleolin accumulation. To further address the transcriptional mechanism of nucleolin in lung cancer formation, we analyze the promoter of nucleolin and found 5 Sp1 binding site on the promoter of nucleolin. Deletion of promoter sequence that contain Sp1 binding sites significantly decrease nucleolin transcriptional activity. Moreover, overexpression of Sp1 will induce nucleolin up-regulation. Finally, the protein level of nucleolin in EGFR (exon19 deletion)-driven lung cancer transgenic mice highly increased. These results will let us to understand the transcriptional mechanism of nucleolin in lung cancer tumorigenesis clearly and benefit to lung cancer study.

目錄
摘要	II
Abstract	IV
誌謝	VI
縮寫檢索表	VII
目錄	IX
第一章 序論	1
1.前言	1
2.肺癌	1
2-1肺癌定義	1
2-2肺癌中的基因突變	2
2-3肺癌中 Kras、EGFR 基因突變	3
3.Nucleolin	5
3-1 Nucleolin之結構及功能簡介	5
3-2 Nucleolin 與腫瘤的關連性	6
3-3片段化的 nucleolin (c-nucleolin)	6
4.Sp1	6
5.研究目標	7
第二章 實驗材料	8
1.化學試劑	8
2.試劑組	10
3.抗生素	11
4.抗體	11
5.細胞培養相關物品	12
5-1細胞培養液	12
5-2 細胞培養相關材料	12
6.實驗用器材	13
7.其他實驗相關器材	13
第三章 實驗方法	14
1.細胞株的培養	14
1-1.細胞種類	14
1-2.培養方式	15
1-3.繼代培養(subculture)	15
2.條件式基因轉殖鼠(conditional transgenic mice)	15
2-1.條件式Kras基因轉殖鼠(Condition Kras activated transgenic mice)原理	15
2-2.條件式EGFR基因轉殖鼠(Condition EGFR activated transgenic mice)原理	16
2-3 .PCR基因定型 (PCR genotyping)	16
3.蛋白質分析(Protein level analysis)	18
3-1.全細胞液的抽取 (Total cell lysate extraction)	18
3-2肺組織液的抽取 (Total lung tissue extraction)	18
3-3硫酸十二酯鈉聚丙烯醯胺凝膠法(SDS-PAGE)	19
3-4.濕式蛋白質電泳轉漬法 (Transfer)	21
3-5阻斷 (Blocking)	21
3-6免疫染色 (Immunoblotting)	21
4.DNA level analysis	22
4-1. Cell RNA萃取 (RNA extraction)	22
4-2反轉錄聚合酶連鎖反應 (RT-PCR)	23
4-3.聚合酶連鎖反應 (PCR)條件	23
5.建構載體 (Nucleolin promoter construct)	24
5-1.設計引子	24
5-2.聚合酶連鎖反應 (PCR)條件	24
5-3.yT&A 載體選殖(yT&A cloning)	25
5-4.質體製備 (plasmid preparation)	25
5-5.選殖 cloning	26
6.報導基因測試 (Reporter gene assay)	27
6-1.大量抽取質體DNA (Plasmid)	27
6-2.暫時性轉染 (Transient transfection)	27
6-3.luciferase活性的測定	28
7.點突變質體製備(Site-directed mutagenesis)	29
8.免疫組織染色  (Immunohisochemistry，IHC)	31
8-1.原理	31
8-2.脫蠟	31
8-3.Antigen Retriever	31
8-4.染色 31
9.細胞靜默 Sp1系統(Sp1 knockdown)	32
10.過度表現Sp1系統 (Sp1 overexpression)	33
第四章 實驗結果	34
1.Nucleolin在肺癌形成中會大量累積	34
1-1.Nucleolin在肺癌細胞株中大量表現	34
1-2.Nucleolin在肺癌轉殖鼠中大量表現	34
2 Nucleolin的累積和肺癌預後相關性	36
2-1.Nucleolin在人類肺癌檢體中會大量表現	36
2-2.Nucleolin累積對肺癌病人的預後率呈現負相關	36
3.癌細胞中,EGFR 及Kras路徑會參與調控nucleolin的轉錄活性	36
3-1 Kras及EGFR 路徑的活化或抑制會影響Nucleolin的 mRNA 層次	37
3-2 Kras及EGFR 路徑的活化或抑制會影響Nucleolin的轉錄活性	38
4.癌細胞中, EGFR 及Kras路徑的調控會影響Nucleolin表現量	38
5.肺癌進程中，Sp1 會促進nucleolin 的轉錄活性上升	39
5-1 在A431、H1299細胞株過度表現Sp1會造成nucleolin表現量上升	39
5-2 在A431、H1299細胞株抑制Sp1會造成nucleolin表現量下降	40
5-3 A431經由EGF的處理對nucleolin 啟動子280-750區域的轉錄活性有極大助益	40
5-4 Sp1會透過EGFR及Kras路徑調控nucleolin	41
第五章    實驗討論	43
1.Nucleolin和癌症	43
2.Nucleolin累積的機制	44
3.造成Sp1累積的機轉	45
4.總結	46
第六章 參考文獻	47
 
實驗結果	55
Figure 1	56
Figure 2	57
Figure 3	58
Figure 4	59
Figure 5	60
Figure 6	61
Figure 7	62
Figure 8	63
Figure 9	64
Figure 10	65
Figure 11	66
Figure 12	67
Figure 13	68
Figure 14	69
Figure 15	70
Figure 16	71
Figure 17	72
Figure 18	73
 
附錄	74
Appendix.1	75
Appendix.2	76
Appendix.3	77
Appendix.4	78
Appendix.5	79
Appendix.6	80
Appendix.7	81
Appendix.8	82
Appendix.9	83




                                    

1. Lin YY, Lai YF, Lu HI, Lai YL, Lin CC: Physical Activity Preferences Among Patients With Lung Cancer in Taiwan. Cancer Nurs 2012.
2. Jazieh AR, Bamefleh H, Demirkazik A, Gaafar RM, Geara FB, Javaid M, Khader J, Khodadad K, Omar W, Saadeddin A et al: Modification and implementation of NCCN guidelines on non-small cell lung cancer in the Middle East and North Africa region. J Natl Compr Canc Netw 2010, 8 Suppl 3:S16-21.
3. Gansler T, Ganz PA, Grant M, Greene FL, Johnstone P, Mahoney M, Newman LA, Oh WK, Thomas CR, Jr., Thun MJ et al: Sixty years of CA: a cancer journal for clinicians. CA Cancer J Clin 2010, 60(6):345-350.
4. Arrieta O, Cardona AF, Federico Bramuglia G, Gallo A, Campos-Parra AD, Serrano S, Castro M, Aviles A, Amorin E, Kirchuk R et al: Genotyping non-small cell lung cancer (NSCLC) in Latin America. J Thorac Oncol 2011, 6(11):1955-1959.
5. Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ: Lung cancer in never smokers - A review. Eur J Cancer 2012, 48(9):1299-1311.
6. Wen W, Shu XO, Gao YT, Yang G, Li Q, Li H, Zheng W: Environmental tobacco smoke and mortality in Chinese women who have never smoked: prospective cohort study. BMJ 2006, 333(7564):376.
7. Weiss J, Stinchcombe TE: Treatment of elderly patients with stage IV non-small-cell lung cancer. Expert Rev Anticancer Ther 2012, 12(1):111-120.
8. Subramanian J, Govindan R: Lung cancer in never smokers: a review. J Clin Oncol 2007, 25(5):561-570.
9. Alsamarai S, Libutti SK, Saif MW: Updates in pancreatic neuroendocrine carcinoma. Highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010. JOP 2010, 11(4):336-340.
10. Haber DA, Bell DW, Sordella R, Kwak EL, Godin-Heymann N, Sharma SV, Lynch TJ, Settleman J: Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors. Cold Spring Harb Symp Quant Biol 2005, 70:419-426.
11. Hwang SJ, Cheng LS, Lozano G, Amos CI, Gu X, Strong LC: Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk. Hum Genet 2003, 113(3):238-243.
12. Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba, II, Fong KM, Toyooka S, Shimizu N et al: Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005, 65(5):1642-1646.
13. Suzuki M, Shigematsu H, Hiroshima K, Iizasa T, Nakatani Y, Minna JD, Gazdar AF, Fujisawa T: Epidermal growth factor receptor expression status in lung cancer correlates with its mutation. Hum Pathol 2005, 36(10):1127-1134.
14. Jia XL, Chen G: EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung. Lung Cancer 2011, 74(3):396-400.
15. Mitsudomi T, Yatabe Y: Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 2010, 277(2):301-308.
16. van Zandwijk N, Mathy A, Boerrigter L, Ruijter H, Tielen I, de Jong D, Baas P, Burgers S, Nederlof P: EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer. Ann Oncol 2007, 18(1):99-103.
17. Takahashi K, Kohno T, Matsumoto S, Nakanishi Y, Arai Y, Yamamoto S, Fujiwara T, Tanaka N, Yokota J: Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells. Clin Cancer Res 2007, 13(1):111-120.
18. Heukamp LC, Buttner R: [Molecular diagnostics in lung carcinoma for therapy stratification]. Pathologe 2010, 31(1):22-28.
19. Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH: p14ARF links the tumour suppressors RB and p53. Nature 1998, 395(6698):124-125.
20. Franklin WA, Veve R, Hirsch FR, Helfrich BA, Bunn PA, Jr.: Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol 2002, 29(1 Suppl 4):3-14.
21. Sundaram MV: RTK/Ras/MAPK signaling. WormBook 2006:1-19.
22. Pierce KL, Luttrell LM, Lefkowitz RJ: New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades. Oncogene 2001, 20(13):1532-1539.
23. Dykhno A, Kostyleva OI, Gershtein ES, Polotskii BE, Kushlinskii NE: [Epidermal growth factor receptors and their ligands in non-small-cell lung carcinoma]. Vestn Ross Akad Med Nauk 1998(5):51-54.
24. Miller WE, Raab-Traub N: The EGFR as a target for viral oncoproteins. Trends Microbiol 1999, 7(11):453-458.
25. Arteaga CL: EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans. Cancer Cell 2006, 9(6):421-423.
26. Baselga J: A review of EGFR targeted therapy. Clin Adv Hematol Oncol 2003, 1(4):218-219.
27. Colabufo NA, Contino M, Niso M, Berardi F, Leopoldo M, Perrone R: EGFR tyrosine kinase inhibitors and multidrug resistance: perspectives. Front Biosci 2011, 16:1811-1823.
28. D'Incecco A, Cappuzzo F: Gefitinib for non-small-cell lung cancer treatment. Expert Opin Drug Saf 2011, 10(6):987-996.
29. Takeda M, Okamoto I, Tsurutani J, Oiso N, Kawada A, Nakagawa K: Clinical Impact of Switching to a Second EGFR-TKI After a Severe AE Related to a First EGFR-TKI in EGFR-mutated NSCLC. Jpn J Clin Oncol 2012, 42(6):528-533.
30. Amler LC, Goddard AD, Hillan KJ: Predicting clinical benefit in non-small-cell lung cancer patients treated with epidermal growth factor tyrosine kinase inhibitors. Cold Spring Harb Symp Quant Biol 2005, 70:483-488.
31. Herbst RS, Kies MS: Gefitinib: current and future status in cancer therapy. Clin Adv Hematol Oncol 2003, 1(8):466-472.
32. Bonaccorsi L, Marchiani S, Muratori M, Forti G, Baldi E: Gefitinib ('IRESSA', ZD1839) inhibits EGF-induced invasion in prostate cancer cells by suppressing PI3 K/AKT activation. J Cancer Res Clin Oncol 2004, 130(10):604-614.
33. Arslan MA, Kutuk O, Basaga H: Protein kinases as drug targets in cancer. Curr Cancer Drug Targets 2006, 6(7):623-634.
34. Ferrer-Soler L, Vazquez-Martin A, Brunet J, Menendez JA, De Llorens R, Colomer R: An update of the mechanisms of resistance to EGFR-tyrosine kinase inhibitors in breast cancer: Gefitinib (Iressa) -induced changes in the expression and nucleo-cytoplasmic trafficking of HER-ligands (Review). Int J Mol Med 2007, 20(1):3-10.
35. Tortora G, Bianco R, Daniele G, Ciardiello F, McCubrey JA, Ricciardi MR, Ciuffreda L, Cognetti F, Tafuri A, Milella M: Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat 2007, 10(3):81-100.
36. Silvestris N, Tommasi S, Santini D, Russo A, Simone G, Petriella D, Maiello E, Tonini G, Colucci G: KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue. Expert Opin Biol Ther 2009, 9(5):565-577.
37. Weickhardt AJ, Tebbutt NC, Mariadason JM: Strategies for overcoming inherent and acquired resistance to EGFR inhibitors by targeting downstream effectors in the RAS/PI3K pathway. Curr Cancer Drug Targets 2010, 10(8):824-833.
38. Wu CC, Hsu HY, Liu HP, Chang JW, Chen YT, Hsieh WY, Hsieh JJ, Hsieh MS, Chen YR, Huang SF: Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications. Cancer 2008, 113(11):3199-3208.
39. Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba, II, Fong KM, Lee H, Toyooka S, Shimizu N et al: Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005, 97(5):339-346.
40. Agrawal AG, Somani RR: Farnesyltransferase inhibitor as anticancer agent. Mini Rev Med Chem 2009, 9(6):638-652.
41. Lebowitz PF, Sakamuro D, Prendergast GC: Farnesyl transferase inhibitors induce apoptosis of Ras-transformed cells denied substratum attachment. Cancer Res 1997, 57(4):708-713.
42. Weber F, Siska P, Kramer M, Zulehner N, Hackl S, Wesierska-Gadek J: Combining an FPTase inhibitor with cisplatin facilitates induction of apoptosis in human A549 lung cancer cells. J Exp Ther Oncol 2011, 9(1):53-65.
43. McGuire TF, Qian Y, Blaskovich MA, Fossum RD, Sun J, Marlowe T, Corey SJ, Wathen SP, Vogt A, Hamilton AD et al: CAAX peptidomimetic FTI-244 decreases platelet-derived growth factor receptor tyrosine phosphorylation levels and inhibits stimulation of phosphatidylinositol 3-kinase but not mitogen-activated protein kinase. Biochem Biophys Res Commun 1995, 214(1):295-303.
44. Lantry LE, Zhang Z, Yao R, Crist KA, Wang Y, Ohkanda J, Hamilton AD, Sebti SM, Lubet RA, You M: Effect of farnesyltransferase inhibitor FTI-276 on established lung adenomas from A/J mice induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Carcinogenesis 2000, 21(1):113-116.
45. Orrick LR, Olson MO, Busch H: Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc Natl Acad Sci U S A 1973, 70(5):1316-1320.
46. Mongelard F, Bouvet P: Nucleolin: a multiFACeTed protein. Trends Cell Biol 2007, 17(2):80-86.
47. Ugrinova I, Monier K, Ivaldi C, Thiry M, Storck S, Mongelard F, Bouvet P: Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol Biol 2007, 8:66.
48. Ginisty H, Sicard H, Roger B, Bouvet P: Structure and functions of nucleolin. J Cell Sci 1999, 112 ( Pt 6):761-772.
49. Sengupta TK, Bandyopadhyay S, Fernandes DJ, Spicer EK: Identification of nucleolin as an AU-rich element binding protein involved in bcl-2 mRNA stabilization. J Biol Chem 2004, 279(12):10855-10863.
50. Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E: Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol 2003, 163(4):871-878.
51. Angelov D, Bondarenko VA, Almagro S, Menoni H, Mongelard F, Hans F, Mietton F, Studitsky VM, Hamiche A, Dimitrov S et al: Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. EMBO J 2006, 25(8):1669-1679.
52. Mi Y, Thomas SD, Xu X, Casson LK, Miller DM, Bates PJ: Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 2003, 278(10):8572-8579.
53. Srivastava M, Pollard HB: Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. FASEB J 1999, 13(14):1911-1922.
54. Zhang J, Tsaprailis G, Bowden GT: Nucleolin stabilizes Bcl-X L messenger RNA in response to UVA irradiation. Cancer Res 2008, 68(4):1046-1054.
55. Pich A, Chiusa L, Margaria E: Prognostic relevance of AgNORs in tumor pathology. Micron 2000, 31(2):133-141.
56. Hoja-Lukowicz D, Przybylo M, Pochec E, Drabik A, Silberring J, Kremser M, Schadendorf D, Laidler P, Litynska A: The new face of nucleolin in human melanoma. Cancer Immunol Immunother 2009, 58(9):1471-1480.
57. Gattoni-Celli S, Buckner CL, Lazarchick J, Stuart RK, Fernandes DJ: Overexpression of nucleolin in engrafted acute myelogenous leukemia cells. Am J Hematol 2009, 84(8):535-538.
58. Grinstein E, Wernet P, Snijders PJ, Rosl F, Weinert I, Jia W, Kraft R, Schewe C, Schwabe M, Hauptmann S et al: Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer. J Exp Med 2002, 196(8):1067-1078.
59. Tulchin N, Chambon M, Juan G, Dikman S, Strauchen J, Ornstein L, Billack B, Woods NT, Monteiro AN: BRCA1 protein and nucleolin colocalize in breast carcinoma tissue and cancer cell lines. Am J Pathol 2010, 176(3):1203-1214.
60. Inder KL, Hill MM, Hancock JF: Nucleophosmin and nucleolin regulate K-Ras signaling. Commun Integr Biol 2010, 3(2):188-190.
61. Fogal V, Sugahara KN, Ruoslahti E, Christian S: Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature. Angiogenesis 2009, 12(1):91-100.
62. Watanabe T, Hirano K, Takahashi A, Yamaguchi K, Beppu M, Fujiki H, Suganuma M: Nucleolin on the cell surface as a new molecular target for gastric cancer treatment. Biol Pharm Bull 2010, 33(5):796-803.
63. Soundararajan S, Chen W, Spicer EK, Courtenay-Luck N, Fernandes DJ: The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res 2008, 68(7):2358-2365.
64. Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM, Jr., Ivanova MM, Bates PJ, Appana SN et al: Identification and Characterization of Nucleolin as a COUP-TFII Coactivator of Retinoic Acid Receptor beta Transcription in Breast Cancer Cells. PLoS One 2012, 7(5):e38278.
65. Teng Y, Girvan AC, Casson LK, Pierce WM, Jr., Qian M, Thomas SD, Bates PJ: AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res 2007, 67(21):10491-10500.
66. Mongelard F, Bouvet P: AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr Opin Mol Ther 2010, 12(1):107-114.
67. Pasternack MS, Bleier KJ, McInerney TN: Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. J Biol Chem 1991, 266(22):14703-14708.
68. Fahling M, Steege A, Perlewitz A, Nafz B, Mrowka R, Persson PB, Thiele BJ: Role of nucleolin in posttranscriptional control of MMP-9 expression. Biochim Biophys Acta 2005, 1731(1):32-40.
69. Lee YH, Mungunsukh O, Tutino RL, Marquez AP, Day RM: Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells. J Cell Sci 2010, 123(Pt 10):1634-1643.
70. Barrera-Saldana H, Takahashi K, Vigneron M, Wildeman A, Davidson I, Chambon P: All six GC-motifs of the SV40 early upstream element contribute to promoter activity in vivo and in vitro. EMBO J 1985, 4(13B):3839-3849.
71. Kang HS, Eshbach TB, White DA, Levine AJ: Deoxyribonucleic acid replication in simian virus 40-infected cells. IV. Two different requirements for protein synthesis during simian virus 40 deoxyribonucleic acid replication. J Virol 1971, 7(1):112-120.
72. Anderson CW, Gesteland RF: Pattern of protein synthesis in monkey cells infected by simian virus 40. J Virol 1972, 9(5):758-765.
73. Emili A, Greenblatt J, Ingles CJ: Species-specific interaction of the glutamine-rich activation domains of Sp1 with the TATA box-binding protein. Mol Cell Biol 1994, 14(3):1582-1593.
74. Safe S, Abdelrahim M: Sp transcription factor family and its role in cancer. Eur J Cancer 2005, 41(16):2438-2448.
75. Wang XB, Peng WQ, Yi ZJ, Zhu SL, Gan QH: [Expression and prognostic value of transcriptional factor sp1 in breast cancer]. Ai Zheng 2007, 26(9):996-1000.
76. Li L, Davie JR: The role of Sp1 and Sp3 in normal and cancer cell biology. Ann Anat 2010, 192(5):275-283.
77. Sankpal UT, Goodison S, Abdelrahim M, Basha R: Targeting Sp1 transcription factors in prostate cancer therapy. Med Chem 2011, 7(5):518-525.
78. Black AR, Black JD, Azizkhan-Clifford J: Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001, 188(2):143-160.
79. Bose SK, Sengupta TK, Bandyopadhyay S, Spicer EK: Identification of Ebp1 as a component of cytoplasmic bcl-2 mRNP (messenger ribonucleoprotein particle) complexes. Biochem J 2006, 396(1):99-107.
80. Fujie Y, Yamamoto H, Ngan CY, Takagi A, Hayashi T, Suzuki R, Ezumi K, Takemasa I, Ikeda M, Sekimoto M et al: Oxaliplatin, a potent inhibitor of survivin, enhances paclitaxel-induced apoptosis and mitotic catastrophe in colon cancer cells. Jpn J Clin Oncol 2005, 35(8):453-463.
81. Zhang D, Cao D, Russell R, Pizzorno G: p53-dependent suppression of uridine phosphorylase gene expression through direct promoter interaction. Cancer Res 2001, 61(18):6899-6905.
82. Otake Y, Sengupta TK, Bandyopadhyay S, Spicer EK, Fernandes DJ: Drug-induced destabilization of bcl-2 mRNA: a new approach for inducing apoptosis in tumor cells. Curr Opin Investig Drugs 2004, 5(6):616-622.
83. Guo J, Zhang K, Ji Y, Jiang X, Zuo S: Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. J Huazhong Univ Sci Technolog Med Sci 2008, 28(3):281-283.
84. Takagi M, Absalon MJ, McLure KG, Kastan MB: Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell 2005, 123(1):49-63.
85. Barbacid M: Opening a New GATAway for Treating KRAS-Driven Lung Tumors. Cancer Cell 2012, 21(5):598-600.
86. Chuang JY, Wang YT, Yeh SH, Liu YW, Chang WC, Hung JJ: Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis. Mol Biol Cell 2008, 19(3):1139-1151.
87. Adhikary S, Eilers M: Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005, 6(8):635-645.
88. Adhikary S, Marinoni F, Hock A, Hulleman E, Popov N, Beier R, Bernard S, Quarto M, Capra M, Goettig S et al: The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell 2005, 123(3):409-421.
89. Milanini-Mongiat J, Pouyssegur J, Pages G: Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription. J Biol Chem 2002, 277(23):20631-20639.

校內：2014-08-14公開
校外：2014-08-14公開

簡易檢索 / 詳目顯示

相關論文