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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 李明學(Ming-Shyue Lee) | |
| dc.contributor.author | Chia-Hao Lin | en |
| dc.contributor.author | 林嘉豪 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:54:48Z | - |
| dc.date.available | 2009-09-15 | |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-06-30 | |
| dc.identifier.citation | 1. Jemal, A., et al., Cancer statistics, 2008. CA Cancer J Clin, 2008. 58(2): p. 71-96.
2. Herbst, R.S., J.V. Heymach, and S.M. Lippman, Lung cancer. N Engl J Med, 2008. 359(13): p. 1367-80. 3. Wistuba, II, et al., Molecular changes in the bronchial epithelium of patients with small cell lung cancer. Clin Cancer Res, 2000. 6(7): p. 2604-10. 4. Soda, M., et al., Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 2007. 448(7153): p. 561-6. 5. Sato, M., et al., A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol, 2007. 2(4): p. 327-43. 6. Beau-Faller, M., et al., MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J Thorac Oncol, 2008. 3(4): p. 331-9. 7. Sun, S., J.H. Schiller, and A.F. Gazdar, Lung cancer in never smokers--a different disease. Nat Rev Cancer, 2007. 7(10): p. 778-90. 8. Spira, A., et al., Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A, 2004. 101(27): p. 10143-8. 9. Zudaire, I., et al., Molecular characterization of small peripheral lung tumors based on the analysis of fine needle aspirates. Histol Histopathol, 2008. 23(1): p. 33-40. 10. Sharma, S.V., et al., Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer, 2007. 7(3): p. 169-81. 11. Chambers, A.F., A.C. Groom, and I.C. MacDonald, Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer, 2002. 2(8): p. 563-72. 12. Friedl, P. and K. Wolf, Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer, 2003. 3(5): p. 362-74. 13. Lauffenburger, D.A. and A.F. Horwitz, Cell migration: a physically integrated molecular process. Cell, 1996. 84(3): p. 359-69. 14. Thiery, J.P., Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2002. 2(6): p. 442-54. 15. Lochter, A., et al., alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol Biol Cell, 1999. 10(2): p. 271-82. 16. Thiery, J.P. and J.P. Sleeman, Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006. 7(2): p. 131-42. 17. Brabletz, T., et al., Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs, 2005. 179(1-2): p. 56-65. 18. Moll, R., et al., Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol, 1993. 143(6): p. 1731-42. 19. Tarin, D., E.W. Thompson, and D.F. Newgreen, The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res, 2005. 65(14): p. 5996-6000; discussion 6000-1. 20. McCrea, P.D. and B.M. Gumbiner, Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem, 1991. 266(7): p. 4514-20. 21. McCrea, P.D., C.W. Turck, and B. Gumbiner, A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science, 1991. 254(5036): p. 1359-61. 22. Huber, A.H., W.J. Nelson, and W.I. Weis, Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell, 1997. 90(5): p. 871-82. 23. Schmalhofer, O., S. Brabletz, and T. Brabletz, E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev, 2009. 28(1-2): p. 151-66. 24. Perez-Moreno, M. and E. Fuchs, Catenins: keeping cells from getting their signals crossed. Dev Cell, 2006. 11(5): p. 601-12. 25. Wehrli, M., et al., arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature, 2000. 407(6803): p. 527-30. 26. Pinson, K.I., et al., An LDL-receptor-related protein mediates Wnt signalling in mice. Nature, 2000. 407(6803): p. 535-8. 27. Yanagawa, S., et al., The dishevelled protein is modified by wingless signaling in Drosophila. Genes Dev, 1995. 9(9): p. 1087-97. 28. Korinek, V., et al., Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science, 1997. 275(5307): p. 1784-7. 29. Behrens, J., et al., Functional interaction of beta-catenin with the transcription factor LEF-1. Nature, 1996. 382(6592): p. 638-42. 30. Shimomura, T., et al., A novel protease obtained from FBS-containing culture supernatant, that processes single chain form hepatocyte growth factor to two chain form in serum-free culture. Cytotechnology, 1992. 8(3): p. 219-29. 31. Miyazawa, K., et al., Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. J Biol Chem, 1993. 268(14): p. 10024-8. 32. Shimomura, T., et al., Activation of the zymogen of hepatocyte growth factor activator by thrombin. J Biol Chem, 1993. 268(30): p. 22927-32. 33. Moriyama, T., et al., Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. FEBS Lett, 1995. 372(1): p. 78-82. 34. Parr, C. and W.G. Jiang, Expression of hepatocyte growth factor/scatter factor, its activator, inhibitors and the c-Met receptor in human cancer cells. Int J Oncol, 2001. 19(4): p. 857-63. 35. Kataoka, H., et al., Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. Cancer Res, 2000. 60(21): p. 6148-59. 36. Nagata, K., et al., Expression of hepatocyte growth factor activator and hepatocyte growth factor activator inhibitor type 1 in human hepatocellular carcinoma. Biochem Biophys Res Commun, 2001. 289(1): p. 205-11. 37. Shimomura, T., et al., Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator. Eur J Biochem, 1995. 229(1): p. 257-61. 38. Lee, S.L., R.B. Dickson, and C.Y. Lin, Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J Biol Chem, 2000. 275(47): p. 36720-5. 39. Miyazawa, K., T. Shimomura, and N. Kitamura, Activation of hepatocyte growth factor in the injured tissues is mediated by hepatocyte growth factor activator. J Biol Chem, 1996. 271(7): p. 3615-8. 40. Shimomura, T., et al., Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor. J Biol Chem, 1997. 272(10): p. 6370-6. 41. Gohda, E., et al., Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest, 1988. 81(2): p. 414-9. 42. Zarnegar, R. and G. Michalopoulos, Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res, 1989. 49(12): p. 3314-20. 43. Nakamura, T., et al., Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett, 1987. 224(2): p. 311-6. 44. Jeffers, M., S. Rong, and G.F. Vande Woude, Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol Cell Biol, 1996. 16(3): p. 1115-25. 45. Li, Y., et al., The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy. Cancer Res, 2005. 65(20): p. 9355-62. 46. Sonnenberg, E., et al., Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol, 1993. 123(1): p. 223-35. 47. Stoker, M., et al., Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature, 1987. 327(6119): p. 239-42. 48. Smrcka, A.V., et al., Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. Science, 1991. 251(4995): p. 804-7. 49. Di Renzo, M.F., et al., Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene, 1991. 6(11): p. 1997-2003. 50. Comoglio, P.M. and C. Boccaccio, The HGF receptor family: unconventional signal transducers for invasive cell growth. Genes Cells, 1996. 1(4): p. 347-54. 51. Comoglio, P.M., Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells. EXS, 1993. 65: p. 131-65. 52. Houldsworth, J., et al., Gene amplification in gastric and esophageal adenocarcinomas. Cancer Res, 1990. 50(19): p. 6417-22. 53. Kuniyasu, H., et al., Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem Biophys Res Commun, 1992. 189(1): p. 227-32. 54. Hara, T., et al., Amplification of c-myc, K-sam, and c-met in gastric cancers: detection by fluorescence in situ hybridization. Lab Invest, 1998. 78(9): p. 1143-53. 55. Miller, C.T., et al., Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma. Oncogene, 2006. 25(3): p. 409-18. 56. Tong, C.Y., et al., Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. J Neurosurg, 2004. 100(2 Suppl Pediatrics): p. 187-93. 57. Bean, J., et al., MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A, 2007. 104(52): p. 20932-7. 58. Ma, P.C., et al., c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev, 2003. 22(4): p. 309-25. 59. Maulik, G., et al., Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev, 2002. 13(1): p. 41-59. 60. Comoglio, P.M., Pathway specificity for Met signalling. Nat Cell Biol, 2001. 3(7): p. E161-2. 61. Comoglio, P.M. and L. Trusolino, Invasive growth: from development to metastasis. J Clin Invest, 2002. 109(7): p. 857-62. 62. Rosario, M. and W. Birchmeier, How to make tubes: signaling by the Met receptor tyrosine kinase. Trends Cell Biol, 2003. 13(6): p. 328-35. 63. Itoh, H., et al., Upregulation of HGF activator inhibitor type 1 but not type 2 along with regeneration of intestinal mucosa. Am J Physiol Gastrointest Liver Physiol, 2000. 278(4): p. G635-43. 64. Kawaguchi, T., et al., Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor. J Biol Chem, 1997. 272(44): p. 27558-64. 65. Marlor, C.W., et al., Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains. J Biol Chem, 1997. 272(18): p. 12202-8. 66. Muller-Pillasch, F., et al., Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer. Biochim Biophys Acta, 1998. 1395(1): p. 88-95. 67. Laskowski, M., Jr. and I. Kato, Protein inhibitors of proteinases. Annu Rev Biochem, 1980. 49: p. 593-626. 68. Qin, L., et al., Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2. FEBS Lett, 1998. 436(1): p. 111-4. 69. Delaria, K.A., et al., Characterization of placental bikunin, a novel human serine protease inhibitor. J Biol Chem, 1997. 272(18): p. 12209-14. 70. Kataoka, H., et al., Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. Cancer Metastasis Rev, 2003. 22(2-3): p. 223-36. 71. Kirchhofer, D., et al., Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2. FEBS Lett, 2005. 579(9): p. 1945-50. 72. Sidenius, N. and F. Blasi, The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy. Cancer Metastasis Rev, 2003. 22(2-3): p. 205-22. 73. Rajapakse, S., et al., Biochemical characterization of human kallikrein 8 and its possible involvement in the degradation of extracellular matrix proteins. FEBS Lett, 2005. 579(30): p. 6879-84. 74. Kapadia, C., et al., Human kallikrein 13 involvement in extracellular matrix degradation. Biochem Biophys Res Commun, 2004. 323(3): p. 1084-90. 75. Parr, C., et al., The hepatocyte growth factor regulatory factors in human breast cancer. Clin Cancer Res, 2004. 10(1 Pt 1): p. 202-11. 76. Yamauchi, M., et al., Hepatocyte growth factor activator inhibitor types 1 and 2 are expressed by tubular epithelium in kidney and down-regulated in renal cell carcinoma. J Urol, 2004. 171(2 Pt 1): p. 890-6. 77. Morris, M.R., et al., Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer Res, 2005. 65(11): p. 4598-606. 78. Hamasuna, R., et al., Reduced expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) in human glioblastomas: implication for anti-invasive role of HAI-2/PB in glioblastoma cells. Int J Cancer, 2001. 93(3): p. 339-45. 79. Schuster, J.M., M. Longo, and P.S. Nelson, Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment. J Neurooncol, 2003. 64(3): p. 219-25. 80. Parr, C. and W.G. Jiang, Hepatocyte growth factor activation inhibitors (HAI-1 and HAI-2) regulate HGF-induced invasion of human breast cancer cells. Int J Cancer, 2006. 119(5): p. 1176-83. 81. Kongkham, P.N., et al., An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res, 2008. 68(23): p. 9945-53. 82. Mitchell, K.J., et al., Functional analysis of secreted and transmembrane proteins critical to mouse development. Nat Genet, 2001. 28(3): p. 241-9. 83. Chu, Y.W., et al., Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol, 1997. 17(3): p. 353-60. 84. Generali, D., et al., Regulation of hepatocyte growth factor activator inhibitor 2 by hypoxia in breast cancer. Clin Cancer Res, 2007. 13(2 Pt 1): p. 550-8. 85. Chen, S.Y. and H.C. Chen, Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion. Mol Cell Biol, 2006. 26(13): p. 5155-67. 86. Rasola, A., et al., A positive feedback loop between hepatocyte growth factor receptor and beta-catenin sustains colorectal cancer cell invasive growth. Oncogene, 2007. 26(7): p. 1078-87. 87. Klein, P.S. and D.A. Melton, A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A, 1996. 93(16): p. 8455-9. 88. Stambolic, V., L. Ruel, and J.R. Woodgett, Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol, 1996. 6(12): p. 1664-8. 89. Lilien, J. and J. Balsamo, The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin. Curr Opin Cell Biol, 2005. 17(5): p. 459-65. 90. Nelson, W.J. and R. Nusse, Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 2004. 303(5663): p. 1483-7. 91. Fukai, K., et al., Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma. Cancer Res, 2003. 63(24): p. 8674-9. 92. Betsunoh, H., et al., Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma. Cancer Sci, 2007. 98(4): p. 491-8. 93. Tung, E.K., et al., HAI-2 is epigenetically downregulated in human hepatocellular carcinoma, and its Kunitz domain type 1 is critical for anti-invasive functions. Int J Cancer, 2009. 124(8): p. 1811-9. 94. Phiel, C.J. and P.S. Klein, Molecular targets of lithium action. Annu Rev Pharmacol Toxicol, 2001. 41: p. 789-813. 95. Williams, R., et al., A molecular cell biology of lithium. Biochem Soc Trans, 2004. 32(Pt 5): p. 799-802. 96. Takeuchi, T., M.A. Shuman, and C.S. Craik, Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Proc Natl Acad Sci U S A, 1999. 96(20): p. 11054-61. 97. Tang, T., et al., Testisin, a glycosyl-phosphatidylinositol-linked serine protease, promotes malignant transformation in vitro and in vivo. Cancer Res, 2005. 65(3): p. 868-78. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43406 | - |
| dc.description.abstract | 在全世界因癌症所造成的死亡中，肺癌佔了最大的部分。肺癌可分為兩種主要的型態，包括非小型細胞肺癌(約佔所有肺癌的百分之八十五)以及小型細胞肺癌(約佔所有肺癌的百分之十五)。儘管有早期預防性的健康檢查及標準的肺癌治療流程，非小型細胞肺癌通常在肺癌的後期才被診斷出，且常伴隨著高度的轉移能力以及很差的預後情況。因此，對於非小型細胞肺癌產生的機制及其惡化的過程，迫切的需要被了解，以期對此病症建立並提供有效的治療方式。第二型肝細胞生長因子活化抑制者(HAI-2)，被認為可以有效降低神經膠質瘤(glioma)以及乳癌(breast cancer)細胞的轉移能力。HAI-2具有兩個Kunitz domain，可以廣泛地抑制絲胺酸蛋白脢，例如plasmin、trypsin及kallikreins等。為了更進一步探討HAI-2在非小型肺癌細胞移動與侵襲中所扮演的角色，我們使用一套由台大醫學院楊泮池院長建構出可模擬非小型肺癌細胞惡化轉移的細胞模式進行研究，包括具低侵略性的CL1-0細胞以及高侵略性的CL1-5細胞。
我們發現，隨著非小型肺癌細胞移動侵襲能力的增強，HAI-2基因的表現就愈低。當過量表現HAI-2在CL1-5細胞時，可抑制細胞移動(migration)與侵襲(invasion)的能力。當在CL1-0細胞降低HAI-2的表現量，則會增加細胞移動及侵襲力。更進一步地，我們發現相較於CL1-0細胞，CL1-5細胞的c-Met、Akt、PDK1及GSK-3β的磷酸化和beta-catenin及FAK的蛋白質表現量都有明顯的上升。相當有趣的是，在CL1-5細胞中過量表現HAI-2時，c-Met、Akt、PDK1及GSK-3beta的磷酸化和beta-catenin及FAK的蛋白質表現量都有明顯的下降。我們更進一步地觀察到，HAI-2的每一個domain對於抑制細胞侵襲的功能都需參與。但在HAI-2抑制細胞移動的過程中，第二個Kunitz domain則扮演一個重要的角色。綜合以上，我們的結果證實肺癌細胞惡化過程，會降低HAI-2表現，以增進其移動侵襲能力。HAI-2表現則可以透過調控c-Met、PDK1、GSK-3beta/Akt的活性及beta-catenin和FAK量，以降低非小型肺癌細胞的移動侵襲與轉移能力。 | zh_TW |
| dc.description.abstract | Lung cancer is the leading cause of cancer deaths in the worldwide and Taiwan. The two major forms of lung cancer are non-small cell lung cancer (about 85% of all lung cancers) and small-cell lung cancer (about 15%). Despite advances in early detection and standard treatment, non-small cell lung cancer is often diagnosed at an advanced stage with a highly metastatic potential and a poor prognosis. Hepatocyte growth factor activator inhibitor type-2 (HAI-2) is proposed to be involved in anti-invasion and anti-metastasis in human glioma and breast cancer, and functions as a serine protease inhibitor with two Kunitz-domains. HAI-2 has broad inhibitory spectra against various serine proteases including hepatocyte growth factor activator, plasmin, trypsin and kallikreins. To further explore the role of HAI-2 in the progression and malignance of non-small cell lung carcinoma (NSCLC) cell migration and invasion, in the current study, we examined the role of HAI-2 in the progression of NSCLC, by using a NSCLC progression model including lowly invasive CL1-0 cells and highly invasive CL1-5 cells, established by Dean Yang.
We found that the gene expression level of HAI-2 was inversely correlated with the cell migration and invasion of NSCLC. Ectopic expression of HAI-2 in CL1-5 cells reduced their cell migration and invasion, while knockdown of HAI-2 in CL1-0 cells promoted those cell migrating and invading capabilities. Moreover, the phosphorylation levels of c-Met, Akt, PDK1 and GSK-3β, as well as the protein levels of FAK and β-catenin were increased in CL1-5 cells, compared to CL1-0 cells. Interestingly, over-expression of HAI-2 in CL1-5 cells reduced the phosphorylation levels of c-Met, Akt, PDK1 and GSK-3β, as well as the protein levels of FAK and β-catenin. Furthermore, we also found that each domain of HAI-2 was important for inhibiting NSCLC cell invasion. The KD2 but not KD1 of HAI-2 played a major role in modulating NSCLC cell migration. The results taken together indicate that HAI-2 plays an inhibitory role in NSCLC cell migration and invasion, at least in part via down-regulating c-Met, PDK1 and Akt/GSK-3β activities, or the protein levels of β-catenin and FAK. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:54:48Z (GMT). No. of bitstreams: 1 ntu-98-R96442013-1.pdf: 2430368 bytes, checksum: 4d39c89fc52a6acd88a5e838c5e0a87f (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | Abstract in Chinese…………………………i
Abstract in English…………………………iii Contents…………………………………………I List of Figures………………………………III Chapter 1. Introduction……………………1 1.1 Lung cancer………………………………2 1.2 Cell migration and invasion……………3 1.3 Molecular signaling of HGF/c-Met……5 1.4 Hepatocyte growth factor activator inhibitors(HAI-1 and HAI-2)………9 1.5 Research motivation and Purpose…………12 Chapter 2. Materials and Methods……………13 2.1 Materials…………………………………14 2.2 Methods……………………………………18 Chapter 3. Results……………………………27 3.1 Role of HAI-2 in cell migration and invasion of NSCLC………………28 3.2 HAI-2 decreased the activity of c-Met in CL1-5 cells……………31 3.3 Role of HAI-2 in FAK………………32 3.4 Epithelial–mesenchymal transition in NSCLC……………………33 3.5 HAI-2 over-expression reduced PI3K/AKT activity…………………34 3.6 HAI-2 reduced the β-catenin expression in CL1-5 cells……………35 3.7 Subcellular localization of β-catenin……36 3.8 Effects of lithium ion on NSCLC cell migration and invasion……37 3.9 Role of HAI-2 in prostate cancer cells………38 3.10 Serine protease in NSCLC cells…………………39 3.11 Expression of HAI-2 in human lung tumors………40 Chapter 4. Discussion……………………………………41 Chapter 5. Figures…………………………………………50 Chapter 6. References……………………………………74 | |
| dc.language.iso | en | |
| dc.subject | 第二型肝細胞生長因子活化抑制者 | zh_TW |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | 細胞侵襲 | zh_TW |
| dc.subject | 細胞移動 | zh_TW |
| dc.subject | c-Met | zh_TW |
| dc.subject | β-catenin | zh_TW |
| dc.subject | β-catenin | en |
| dc.subject | HAI-2 | en |
| dc.subject | c-Met | en |
| dc.subject | lung cancer | en |
| dc.subject | migration | en |
| dc.subject | invasion | en |
| dc.title | 第二型肝細胞生長因子活化抑制者在非小型肺癌細胞移動侵襲中的抑制角色 | zh_TW |
| dc.title | Inhibitory role of hepatocyte growth factor activator inhibitor type 2 in cell migration and invasion of non-small cell lung carcinoma cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊泮池(Pan-Chyr Yang),周綠蘋(Lu-Ping Chow),沈湯龍(Tang-Long Shen,) | |
| dc.subject.keyword | 第二型肝細胞生長因子活化抑制者,肺癌,細胞移動,細胞侵襲,c-Met,β-catenin, | zh_TW |
| dc.subject.keyword | HAI-2,c-Met,lung cancer,migration,invasion,β-catenin, | en |
| dc.relation.page | 88 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-06-30 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| Appears in Collections: | 生物化學暨分子生物學科研究所 | |
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