請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61207完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張鑫(Shin C. Chang) | |
| dc.contributor.author | Ke-Jui Yen | en |
| dc.contributor.author | 嚴可芮 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:53:08Z | - |
| dc.date.available | 2015-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-09 | |
| dc.identifier.citation | Aoudjit, F. and K. Vuori (2001). 'Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells.' Oncogene 20(36): 4995-5004.
Arjonen, A., J. Alanko, S. Veltel and J. Ivaska (2012). 'Distinct recycling of active and inactive beta1 integrins.' Traffic 13(4): 610-625. Bartenschlager, R., M. Frese and T. Pietschmann (2004). 'Novel insights into hepatitis C virus replication and persistence.' Adv Virus Res 63: 71-180. Behrens, S. E., L. Tomei and R. De Francesco (1996). 'Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus.' EMBO J 15(1): 12-22. Bergamini, C., C. Sgarra, P. Trerotoli, L. Lupo, A. Azzariti, S. Antonaci and G. Giannelli (2007). 'Laminin-5 stimulates hepatocellular carcinoma growth through a different function of alpha6beta4 and alpha3beta1 integrins.' Hepatology 46(6): 1801-1809. Blight, K. J. (2011). 'Charged residues in hepatitis C virus NS4B are critical for multiple NS4B functions in RNA replication.' J Virol 85(16): 8158-8171. Borowski, P., R. Kuhl, R. Laufs, J. Schulze zur Wiesch and M. Heiland (1999). 'Identification and characterization of a histone binding site of the non-structural protein 3 of hepatitis C virus.' J Clin Virol 13(1-2): 61-69. Casar, B., I. Rimann, H. Kato, S. J. Shattil, J. P. Quigley and E. I. Deryugina (2012). 'In vivo cleaved CDCP1 promotes early tumor dissemination via complexing with activated beta1 integrin and induction of FAK/PI3K/Akt motility signaling.' Oncogene. Chang, S. C., J. C. Cheng, Y. H. Kou, C. H. Kao, C. H. Chiu, H. Y. Wu and M. F. Chang (2000). 'Roles of the AX(4)GKS and arginine-rich motifs of hepatitis C virus RNA helicase in ATP- and viral RNA-binding activity.' J Virol 74(20): 9732-9737. Chang, S. C., J. H. Yen, H. Y. Kang, M. H. Jang and M. F. Chang (1994). 'Nuclear localization signals in the core protein of hepatitis C virus.' Biochem Biophys Res Commun 205(2): 1284-1290. Cheng, J. C., M. F. Chang and S. C. Chang (1999). 'Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3' end of the viral RNA.' J Virol 73(8): 7044-7049. Cheng, P. L., M. H. Chang, C. H. Chao and Y. H. Lee (2004). 'Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation.' Oncogene 23(47): 7821-7838. Choi, Y. P., B. G. Kim, M. Q. Gao, S. Kang and N. H. Cho (2012). 'Targeting ILK and beta4 integrin abrogates the invasive potential of ovarian cancer.' Biochem Biophys Res Commun 427(3): 642-648. de Chassey, B., V. Navratil, L. Tafforeau, M. S. Hiet, A. Aublin-Gex, S. Agaugue, G. Meiffren, F. Pradezynski, B. F. Faria, T. Chantier, M. Le Breton, J. Pellet, N. Davoust, P. E. Mangeot, A. Chaboud, F. Penin, Y. Jacob, P. O. Vidalain, M. Vidal, P. Andre, C. Rabourdin-Combe and V. Lotteau (2008). 'Hepatitis C virus infection protein network.' Mol Syst Biol 4: 230. Enjoji, M., H. Sakai, M. Nakashima and H. Nawata (1998). 'Integrins: utility as cell type- and stage-specific markers for hepatocellular carcinoma and cholangiocarcinoma.' In Vitro Cell Dev Biol Anim 34(1): 25-27. Enomoto, N., I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, N. Izumi, F. Marumo and C. Sato (1995). 'Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A region.' J Clin Invest 96(1): 224-230. Etienne-Manneville, S. and A. Hall (2002). 'Rho GTPases in cell biology.' Nature 420(6916): 629-635. Feinstone, S. M., A. Z. Kapikian, R. H. Purcell, H. J. Alter and P. V. Holland (1975). 'Transfusion-associated hepatitis not due to viral hepatitis type A or B.' N Engl J Med 292(15): 767-770. Feld, J. J., S. Nanda, Y. Huang, W. Chen, M. Cam, S. N. Pusek, L. M. Schweigler, D. Theodore, S. L. Zacks, T. J. Liang and M. W. Fried (2007). 'Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.' Hepatology 46(5): 1548-1563. Feng, D. Y., Y. Sun, R. X. Cheng, X. M. Ouyang and H. Zheng (2005). 'Effect of hepatitis C virus nonstructural protein NS3 on proliferation and MAPK phosphorylation of normal hepatocyte line.' World J Gastroenterol 11(14): 2157-2161. Fletcher, S. J. and J. Z. Rappoport (2010). 'Moving forward: polarised trafficking in cell migration.' Trends Cell Biol 20(2): 71-78. Friebe, P. and R. Bartenschlager (2002). 'Genetic analysis of sequences in the 3' nontranslated region of hepatitis C virus that are important for RNA replication.' J Virol 76(11): 5326-5338. Fujita, T., S. Ishido, S. Muramatsu, M. Itoh and H. Hotta (1996). 'Suppression of actinomycin D-induced apoptosis by the NS3 protein of hepatitis C virus.' Biochem Biophys Res Commun 229(3): 825-831. Gale, M. J., Jr., M. J. Korth, N. M. Tang, S. L. Tan, D. A. Hopkins, T. E. Dever, S. J. Polyak, D. R. Gretch and M. G. Katze (1997). 'Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein.' Virology 230(2): 217-227. Giannelli, G., C. Bergamini, E. Fransvea, C. Sgarra and S. Antonaci (2005). 'Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal transition in hepatocellular carcinoma.' Gastroenterology 129(5): 1375-1383. Goffard, A., N. Callens, B. Bartosch, C. Wychowski, F. L. Cosset, C. Montpellier and J. Dubuisson (2005). 'Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins.' J Virol 79(13): 8400-8409. Grakoui, A., D. W. McCourt, C. Wychowski, S. M. Feinstone and C. M. Rice (1993). 'Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites.' J Virol 67(5): 2832-2843. Grant, B. D. and J. G. Donaldson (2009). 'Pathways and mechanisms of endocytic recycling.' Nat Rev Mol Cell Biol 10(9): 597-608. Griffin, S. D., L. P. Beales, D. S. Clarke, O. Worsfold, S. D. Evans, J. Jaeger, M. P. Harris and D. J. Rowlands (2003). 'The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine.' FEBS Lett 535(1-3): 34-38. Guo, W. and F. G. Giancotti (2004). 'Integrin signalling during tumour progression.' Nat Rev Mol Cell Biol 5(10): 816-826. Guo, W., Y. Pylayeva, A. Pepe, T. Yoshioka, W. J. Muller, G. Inghirami and F. G. Giancotti (2006). 'Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis.' Cell 126(3): 489-502. Gupta, S. K., S. Oommen, M. C. Aubry, B. P. Williams and N. E. Vlahakis (2013). 'Integrin alpha9beta1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition.' Oncogene 32(2): 141-150. Hassan, M., H. Ghozlan and O. Abdel-Kader (2005). 'Activation of c-Jun NH2-terminal kinase (JNK) signaling pathway is essential for the stimulation of hepatitis C virus (HCV) non-structural protein 3 (NS3)-mediated cell growth.' Virology 333(2): 324-336. Hijikata, M., N. Kato, Y. Ootsuyama, M. Nakagawa and K. Shimotohno (1991). 'Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis.' Proc Natl Acad Sci U S A 88(13): 5547-5551. Honda, M., M. R. Beard, L. H. Ping and S. M. Lemon (1999). 'A phylogenetically conserved stem-loop structure at the 5' border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation.' J Virol 73(2): 1165-1174. Hood, J. D. and D. A. Cheresh (2002). 'Role of integrins in cell invasion and migration.' Nat Rev Cancer 2(2): 91-100. Hughes, P. E. and M. Pfaff (1998). 'Integrin affinity modulation.' Trends Cell Biol 8(9): 359-364. Ishido, S. and H. Hotta (1998). 'Complex formation of the nonstructural protein 3 of hepatitis C virus with the p53 tumor suppressor.' FEBS Lett 438(3): 258-262. Ito, Y., Y. Sasaki, M. Horimoto, S. Wada, Y. Tanaka, A. Kasahara, T. Ueki, T. Hirano, H. Yamamoto, J. Fujimoto, E. Okamoto, N. Hayashi and M. Hori (1998). 'Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma.' Hepatology 27(4): 951-958. Itoh, R. E., K. Kurokawa, Y. Ohba, H. Yoshizaki, N. Mochizuki and M. Matsuda (2002). 'Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells.' Mol Cell Biol 22(18): 6582-6591. Jaffe, A. B. and A. Hall (2005). 'Rho GTPases: biochemistry and biology.' Annu Rev Cell Dev Biol 21: 247-269. Kou, Y. H., M. F. Chang, Y. M. Wang, T. M. Hung and S. C. Chang (2007). 'Differential requirements of NS4A for internal NS3 cleavage and polyprotein processing of hepatitis C virus.' J Virol 81(15): 7999-8008. Kryczka, J., M. Stasiak, L. Dziki, M. Mik, A. Dziki and C. Cierniewski (2012). 'Matrix metalloproteinase-2 cleavage of the beta1 integrin ectodomain facilitates colon cancer cell motility.' J Biol Chem 287(43): 36556-36566. Kuo, G., Q. L. Choo, H. J. Alter, G. L. Gitnick, A. G. Redeker, R. H. Purcell, T. Miyamura, J. L. Dienstag, M. J. Alter, C. E. Stevens and et al. (1989). 'An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis.' Science 244(4902): 362-364. Kwun, H. J., E. Y. Jung, J. Y. Ahn, M. N. Lee and K. L. Jang (2001). 'p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3.' J Gen Virol 82(Pt 9): 2235-2241. Lerat, H., M. Honda, M. R. Beard, K. Loesch, J. Sun, Y. Yang, M. Okuda, R. Gosert, S. Y. Xiao, S. A. Weinman and S. M. Lemon (2002). 'Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus.' Gastroenterology 122(2): 352-365. Macias-Perez, I., C. Borza, X. Chen, X. Yan, R. Ibanez, G. Mernaugh, L. M. Matrisian, R. Zent and A. Pozzi (2008). 'Loss of integrin alpha1beta1 ameliorates Kras-induced lung cancer.' Cancer Res 68(15): 6127-6135. Masumoto, A., S. Arao and M. Otsuki (1999). 'Role of beta1 integrins in adhesion and invasion of hepatocellular carcinoma cells.' Hepatology 29(1): 68-74. Matter, M. L. and E. Ruoslahti (2001). 'A signaling pathway from the alpha5beta1 and alpha(v)beta3 integrins that elevates bcl-2 transcription.' J Biol Chem 276(30): 27757-27763. Miao, H., C. H. Nickel, L. G. Cantley, L. A. Bruggeman, L. N. Bennardo and B. Wang (2003). 'EphA kinase activation regulates HGF-induced epithelial branching morphogenesis.' J Cell Biol 162(7): 1281-1292. Moriya, K., H. Fujie, Y. Shintani, H. Yotsuyanagi, T. Tsutsumi, K. Ishibashi, Y. Matsuura, S. Kimura, T. Miyamura and K. Koike (1998). 'The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice.' Nat Med 4(9): 1065-1067. Nicolson, G. L. and G. Poste (1976). 'The cancer cell: dynamic aspects and modifications in cell-surface organization (first of two parts).' N Engl J Med 295(4): 197-203. Palmer, E. L., C. Ruegg, R. Ferrando, R. Pytela and D. Sheppard (1993). 'Sequence and tissue distribution of the integrin alpha 9 subunit, a novel partner of beta 1 that is widely distributed in epithelia and muscle.' J Cell Biol 123(5): 1289-1297. Pileri, P., Y. Uematsu, S. Campagnoli, G. Galli, F. Falugi, R. Petracca, A. J. Weiner, M. Houghton, D. Rosa, G. Grandi and S. Abrignani (1998). 'Binding of hepatitis C virus to CD81.' Science 282(5390): 938-941. Plow, E. F., T. A. Haas, L. Zhang, J. Loftus and J. W. Smith (2000). 'Ligand binding to integrins.' J Biol Chem 275(29): 21785-21788. Poordad, F., J. McCone, Jr., B. R. Bacon, S. Bruno, M. P. Manns, M. S. Sulkowski, I. M. Jacobson, K. R. Reddy, Z. D. Goodman, N. Boparai, M. J. DiNubile, V. Sniukiene, C. A. Brass, J. K. Albrecht, J. P. Bronowicki and S.-. Investigators (2011). 'Boceprevir for untreated chronic HCV genotype 1 infection.' N Engl J Med 364(13): 1195-1206. Reed, K. E. and C. M. Rice (1999). 'Expression and Characterization of the HCV NS2 Protease.' Methods Mol Med 19: 331-342. Riento, K. and A. J. Ridley (2003). 'Rocks: multifunctional kinases in cell behaviour.' Nat Rev Mol Cell Biol 4(6): 446-456. Sakamuro, D., T. Furukawa and T. Takegami (1995). 'Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells.' J Virol 69(6): 3893-3896. Santolini, E., G. Migliaccio and N. La Monica (1994). 'Biosynthesis and biochemical properties of the hepatitis C virus core protein.' J Virol 68(6): 3631-3641. Scarselli, E., H. Ansuini, R. Cerino, R. M. Roccasecca, S. Acali, G. Filocamo, C. Traboni, A. Nicosia, R. Cortese and A. Vitelli (2002). 'The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.' EMBO J 21(19): 5017-5025. Scatena, M., M. Almeida, M. L. Chaisson, N. Fausto, R. F. Nicosia and C. M. Giachelli (1998). 'NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival.' J Cell Biol 141(4): 1083-1093. Schlaepfer, D. D. and T. Hunter (1997). 'Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src.' J Biol Chem 272(20): 13189-13195. Sheetz, M. P., D. P. Felsenfeld and C. G. Galbraith (1998). 'Cell migration: regulation of force on extracellular-matrix-integrin complexes.' Trends Cell Biol 8(2): 51-54. Shen, B., M. K. Delaney and X. Du (2012). 'Inside-out, outside-in, and inside-outside-in: G protein signaling in integrin-mediated cell adhesion, spreading, and retraction.' Curr Opin Cell Biol 24(5): 600-606. Shoji, I., T. Suzuki, M. Sato, H. Aizaki, T. Chiba, Y. Matsuura and T. Miyamura (1999). 'Internal processing of hepatitis C virus NS3 protein.' Virology 254(2): 315-323. Soriano, V., M. G. Peters and S. Zeuzem (2009). 'New therapies for hepatitis C virus infection.' Clin Infect Dis 48(3): 313-320. Su, J. M., L. Gui, Y. P. Zhou and X. L. Zha (2002). 'Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance.' World J Gastroenterol 8(4): 613-618. Tai, C. L., W. K. Chi, D. S. Chen and L. H. Hwang (1996). 'The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3).' J Virol 70(12): 8477-8484. Tanaka, M., M. Nagano-Fujii, L. Deng, S. Ishido, K. Sada and H. Hotta (2006). 'Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3.' Biochem Biophys Res Commun 340(3): 792-799. Tedbury, P. R. and M. Harris (2007). 'Characterisation of the role of zinc in the hepatitis C virus NS2/3 auto-cleavage and NS3 protease activities.' J Mol Biol 366(5): 1652-1660. Tiwari, S., J. A. Askari, M. J. Humphries and N. J. Bulleid (2011). 'Divalent cations regulate the folding and activation status of integrins during their intracellular trafficking.' J Cell Sci 124(Pt 10): 1672-1680. Torimura, T., T. Ueno, M. Kin, S. Inuzuka, H. Sugawara, S. Tamaki, R. Tsuji, K. Sujaku, M. Sata and K. Tanikawa (1997). 'Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.' Hum Pathol 28(10): 1131-1138. van der Flier, A. and A. Sonnenberg (2001). 'Function and interactions of integrins.' Cell Tissue Res 305(3): 285-298. Verga-Gerard, A., M. Porcherot, L. Meyniel-Schicklin, P. Andre, V. Lotteau and L. Perrin-Cocon (2013). 'Hepatitis C virus/human interactome identifies SMURF2 and the viral protease as critical elements for the control of TGF-beta signaling.' FASEB J. Volpes, R., J. J. van den Oord and V. J. Desmet (1993). 'Integrins as differential cell lineage markers of primary liver tumors.' Am J Pathol 142(5): 1483-1492. Vuori, K. and E. Ruoslahti (1994). 'Association of insulin receptor substrate-1 with integrins.' Science 266(5190): 1576-1578. Webb, D. J., K. Donais, L. A. Whitmore, S. M. Thomas, C. E. Turner, J. T. Parsons and A. F. Horwitz (2004). 'FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly.' Nat Cell Biol 6(2): 154-161. Weis, S. M. and D. A. Cheresh (2011). 'alphaV integrins in angiogenesis and cancer.' Cold Spring Harb Perspect Med 1(1): a006478. Wolk, B., D. Sansonno, H. G. Krausslich, F. Dammacco, C. M. Rice, H. E. Blum and D. Moradpour (2000). 'Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines.' J Virol 74(5): 2293-2304. Wu, Y., J. Zuo, G. Ji, H. Saiyin, X. Liu, F. Yin, N. Cao, Y. Wen, J. J. Li and L. Yu (2009). 'Proapoptotic function of integrin beta(3) in human hepatocellular carcinoma cells.' Clin Cancer Res 15(1): 60-69. Xu, X., Y. M. Li, H. Ji, C. Z. Hou, Y. B. Cheng and F. P. Ma (2005). 'Changes of ECM and CAM gene expression profile in the cirrhotic liver after HCV infection: analysis by cDNA expression array.' World J Gastroenterol 11(14): 2184-2187. Yang, S. H., C. G. Lee, M. K. Song and Y. C. Sung (2000). 'Internal cleavage of hepatitis C virus NS3 protein is dependent on the activity of NS34A protease.' Virology 268(1): 132-140. Yao, M., X. D. Zhou, X. L. Zha, D. R. Shi, J. Fu, J. Y. He, H. F. Lu and Z. Y. Tang (1997). 'Expression of the integrin alpha5 subunit and its mediated cell adhesion in hepatocellular carcinoma.' J Cancer Res Clin Oncol 123(8): 435-440. Yokota, J. (2000). 'Tumor progression and metastasis.' Carcinogenesis 21(3): 497-503. Zein, N. N. (2000). 'Clinical significance of hepatitis C virus genotypes.' Clin Microbiol Rev 13(2): 223-235. Zemel, R., S. Gerechet, H. Greif, L. Bachmatove, Y. Birk, A. Golan-Goldhirsh, M. Kunin, Y. Berdichevsky, I. Benhar and R. Tur-Kaspa (2001). 'Cell transformation induced by hepatitis C virus NS3 serine protease.' J Viral Hepat 8(2): 96-102. Zeuzem, S., P. Andreone, S. Pol, E. Lawitz, M. Diago, S. Roberts, R. Focaccia, Z. Younossi, G. R. Foster, A. Horban, P. Ferenci, F. Nevens, B. Mullhaupt, P. Pockros, R. Terg, D. Shouval, B. van Hoek, O. Weiland, R. Van Heeswijk, S. De Meyer, D. Luo, G. Boogaerts, R. Polo, G. Picchio, M. Beumont and R. S. Team (2011). 'Telaprevir for retreatment of HCV infection.' N Engl J Med 364(25): 2417-2428. Zhou, G. F., F. Ye, L. H. Cao and X. L. Zha (2000). 'Over expression of integrin alpha 5 beta 1 in human hepatocellular carcinoma cell line suppresses cell proliferation in vitro and tumorigenicity in nude mice.' Mol Cell Biochem 207(1-2): 49-55. Zoulim, F., M. Chevallier, M. Maynard and C. Trepo (2003). 'Clinical consequences of hepatitis C virus infection.' Rev Med Virol 13(1): 57-68. 史宗鑫 (2009) C型肝炎病毒NS3蛋白質對焦點黏著訊息傳遞之調控.碩士論文 吳雨柔 (2012) C型肝炎病毒非結構性蛋白質NS3對細胞貼附及移動能力的影響. 碩士論文 許倖慈(2011) C型肝炎病毒非結構性蛋白質NS3對細胞貼附以及integrin訊息傳遞路徑的影響.碩士論文 寇怡衡(2008) 非結構性蛋白質NS3和NS4A參與C型肝炎病毒致病之分子機轉.博士論文 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61207 | - |
| dc.description.abstract | C型肝炎病毒具有單股正向RNA基因體,可以轉譯出一多蛋白質前驅物,並由宿主和病毒蛋白酶切割成結構性和非結構性蛋白質;非結構性蛋白質NS3具有serine protease, RNA helicase和 ATPase的功能。先前研究指出NS3具有oncogenic potential,表現NS3蛋白質能使細胞在沒有貼附以及低血清的環境下穩定生長,也可誘發裸鼠產生腫瘤。本實驗室研究也發現NS3具有內部截切以及細胞轉型的能力,另外,利用共同免疫沉澱法和GST-pull down assay 發現NS3蛋白質和細胞因子integrin β1 有交互作用。已知integrin 是一個細胞表面受器,參與調控細胞的貼附、生長、移動及凋亡,也與癌症的發生和轉移有極大的關聯性。因此,本研究進一步探討NS3對細胞貼附和細胞移動的影響並探討NS3與integrin β1在細胞中分布的位置及兩者間的調節作用。結果發現NS3表現時細胞初期貼附到collagen和fibronectin細胞外基質的能力明顯下降。同時在細胞傷口癒合(wound healing assay)和細胞散射到固定配體(scattering onto immobilized ligands assay)的實驗中,均觀察到NS3對細胞移動有增強的作用。另外,NS3和integrin beta1在細胞中有部分重疊的現象,西方墨點法分析結果顯示NS3蛋白質表現會造成integrin β1活化態比例增加。NS3是否參與integrin的recycling和degradation,藉此調節integrin的表現與活性,造成細胞型態的轉移,影響細胞貼附以及移動,均有待進一步探討。本研究對C型肝炎病毒 NS3蛋白質造成細胞癌化的可能機制提供一個研究的方向。 | zh_TW |
| dc.description.abstract | Hepatitis C virus (HCV) has a positive single-stranded RNA genome. The viral genome can be translated into a polyprotein precursor that is further processed into structural and non-structural proteins. The non-structural protein 3 (NS3) possesses serine protease, RNA helicase and ATPase activities. Previous studies have demonstrated a oncogenic potential of the NS3 protein. Expression of the NS3 protein allowed cells to grow in non-adhered environment and in low serum medium. NS3 can also induce tumor formation in nude mice. In addition, our laboratory has demonstrated an internal NS3 cleavage activity associated with cell transformation. By performing co-immunoprecipitation and GST-pull down assay, our laboratory also identified an interaction between NS3 and integrin β1. Integrin receptors are known to be involved in cell adhesion, growth, migration and apoptosis. Previous studies indicated that changes on the expression level and configuration of integrins have great correlation with cancer progression and metastasis. In this study, the effects of HCV NS3 on cell adhesion and migration and the interplay between the NS3 protein and integrin β1 were further investigated. The results demonstrated that expression of NS3 reduced initial adhesion of cells on fibronectin and collagen. Meanwhile, cell migration was enhanced by NS3 in wound healing and scattering onto immobilized ligands assay. Furthermore, NS3 partially co-localized with endogenous integrin beta1 and up-regulated the ratio of active to total form of integrin β1. Whether NS3 mediates cell adhesion and migration through integrin recycling and degradation remains to be elucidated. This study provides a direction in understanding the possible mechanisms of HCV NS3 protein involved in tumor formation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:53:08Z (GMT). No. of bitstreams: 1 ntu-102-R00445128-1.pdf: 3452133 bytes, checksum: f281b051cb7f2c8cf30c4f33c48be96f (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 摘要… i
Abstract ii 目錄… iii 圖表目錄 v 緒論… 1 一、C型肝炎病毒的歷史 1 二、C型肝炎病毒的現況與治療 1 三、C型肝炎病毒的基因體構造和功能 2 四、非結構性蛋白質NS3的特性 5 五、穿膜受器integrin與訊息傳遞 7 六、Integrin與癌化進程的關係 9 研究目的 11 材料與方法 12 一、藥品 12 二、抗體 13 三、細胞培養液及轉染試劑 14 四、套組試劑 14 五、其他材料 15 六、細胞株 15 七、質體 16 八、細菌轉型 (Transformation) 17 九、DNA 轉染 (DNA transfection) 17 十、細胞全蛋白質收取 17 十一、蛋白質定量 18 十二、正十二烷硫酸鈉–聚丙醯胺板膠電泳 (SDS-polyacrylamide gel electrophoresis, SDS-PAGE) 18 十三、西方墨點法 19 十四、細胞黏著度測試 (Adhesion assay) 19 十五、細胞存活率分析 (MTT assay) 20 十六、細胞傷口癒合分析 (Wound healing assay) 20 十七、細胞散射到固定配體分析 (Scattering onto immobilized ligands assay, SOIL assay) 21 十八、免疫螢光染色 (Immunofluoresence staining) 21 實驗結果 23 一、 NS3蛋白質影響細胞貼附能力 23 二、 NS3蛋白質對細胞存活的影響 24 三、 NS3蛋白質影響細胞移動 25 四、 NS3蛋白質和integrin β1 在細胞分布的情況 26 五、 NS3蛋白質對細胞內生性 integrin β1 表現量的影響 26 討論 29 圖表 33 參考文獻 42 | |
| dc.language.iso | zh-TW | |
| dc.subject | 細胞移動 | zh_TW |
| dc.subject | 細胞貼附 | zh_TW |
| dc.subject | integrin beta1 | zh_TW |
| dc.subject | C型肝炎病毒 | zh_TW |
| dc.subject | hepatitis C virus | en |
| dc.subject | integrin beta1 | en |
| dc.subject | cell Adhesion | en |
| dc.subject | cell migration | en |
| dc.title | C型肝炎病毒NS3與Integrin beta1的交互作用以及對細胞貼附和移動的影響 | zh_TW |
| dc.title | Hepatitis C Virus NS3 Protein Associates with Integrin beta1 and Influences Cell Adhesion and Migration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 董馨蓮(Shin-Lian, Doong),李明學(Ming-Shyue Lee),林素芳(Su-Fang Lin) | |
| dc.subject.keyword | C型肝炎病毒,integrin beta1,細胞貼附,細胞移動, | zh_TW |
| dc.subject.keyword | hepatitis C virus,integrin beta1,cell Adhesion,cell migration, | en |
| dc.relation.page | 50 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位: | 微生物學科所 | |
文件中的檔案:
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-102-1.pdf 未授權公開取用 | 3.37 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。
