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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李明學(Ming-Shyue Lee) | |
dc.contributor.author | Ya-Ting Tu | en |
dc.contributor.author | 塗雅婷 | zh_TW |
dc.date.accessioned | 2021-06-13T15:35:30Z | - |
dc.date.available | 2008-08-13 | |
dc.date.copyright | 2008-08-13 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-11 | |
dc.identifier.citation | [1] Szabo, R., Wu, Q., Dickson, R.B., Netzel-Arnett, S., Antalis, T.M. and Bugge, T.H. (2003). Type II transmembrane serine proteases. Thromb Haemost 90, 185-93.
[2] Shi, Y.E., Torri, J., Yieh, L., Wellstein, A., Lippman, M.E. and Dickson, R.B. (1993). Identification and characterization of a novel matrix-degrading protease from hormone-dependent human breast cancer cells. Cancer Res 53, 1409-15. [3] Lin, C.Y., Anders, J., Johnson, M., Sang, Q.A. and Dickson, R.B. (1999). Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. J Biol Chem 274, 18231-6. [4] Zhang, Y., Cai, X., Schlegelberger, B. and Zheng, S. (1998). Assignment1 of human putative tumor suppressor genes ST13 (alias SNC6) and ST14 (alias SNC19) to human chromosome bands 22q13 and 11q24-->q25 by in situ hybridization. Cytogenet Cell Genet 83, 56-7. [5] Collec, E., Colin, Y., Carbonnet, F., Hattab, C., Bertrand, O., Cartron, J.P. and Kim, C.L. (1999). Structure and expression of the mouse homologue of the XK gene. Immunogenetics 50, 16-21. [6] Kim, M.G., Chen, C., Lyu, M.S., Cho, E.G., Park, D., Kozak, C. and Schwartz, R.H. (1999). Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains. Immunogenetics 49, 420-8. [7] Takeuchi, T., Shuman, M.A. and Craik, C.S. (1999). 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 96, 11054-61. [8] Tanimoto, H., Underwood, L.J., Wang, Y., Shigemasa, K., Parmley, T.H. and O'Brien, T.J. (2001). Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention. Tumour Biol 22, 104-14. [9] Oberst, M.D., Singh, B., Ozdemirli, M., Dickson, R.B., Johnson, M.D. and Lin, C.Y. (2003). Characterization of matriptase expression in normal human tissues. J Histochem Cytochem 51, 1017-25. [10] Kim, C., Cho, Y., Kang, C.H., Kim, M.G., Lee, H., Cho, E.G. and Park, D. (2005). Filamin is essential for shedding of the transmembrane serine protease, epithin. EMBO Rep 6, 1045-51. [11] Oberst, M.D., Williams, C.A., Dickson, R.B., Johnson, M.D. and Lin, C.Y. (2003). The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor. J Biol Chem 278, 26773-9. [12] Eun-Gyung Cho, M.G.K., Chungho Kim, Seung-Ryul Kim, Ihn Sik Seong, Chinha Chung, Ronald H. Schwart, and Dongeun Park. (2001). N-terminal processing is essential for release of epithin, a mouse Type II membrane serine protease. J. Biol. Chem. 276, 44581-44589. [13] Benaud, C., Dickson, R.B. and Lin, C.Y. (2001). Regulation of the activity of matriptase on epithelial cell surfaces by a blood-derived factor. Eur J Biochem 268, 1439-47. [14] Benaud, C., Oberst, M., Hobson, J.P., Spiegel, S., Dickson, R.B. and Lin, C.Y. (2002). Sphingosine 1-phosphate, present in serum-derived lipoproteins, activates matriptase. J Biol Chem 277, 10539-46. [15] Lee, M.S., Kiyomiya, K., Benaud, C., Dickson, R.B. and Lin, C.Y. (2005). Simultaneous activation and hepatocyte growth factor activator inhibitor 1-mediated inhibition of matriptase induced at activation foci in human mammary epithelial cells. Am J Physiol Cell Physiol 288, C932-41. [16] Kiyomiya, K., Lee, M.S., Tseng, I.C., Zuo, H., Barndt, R.J., Johnson, M.D., Dickson, R.B. and Lin, C.Y. (2006). Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells. Am J Physiol Cell Physiol 291, C40-9. [17] Lee, S.L., Dickson, R.B. and Lin, C.Y. (2000). Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J Biol Chem 275, 36720-5. [18] Takeuchi, T., Harris, J.L., Huang, W., Yan, K.W., Coughlin, S.R. and Craik, C.S. (2000). Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. J Biol Chem 275, 26333-42. [19] List, K. et al. (2005). Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev 19, 1934-50. [20] List, K. et al. (2002). Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene 21, 3765-79. [21] List, K., Szabo, R., Molinolo, A., Nielsen, B.S. and Bugge, T.H. (2006). Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis. Am J Pathol 168, 1513-25. [22] List, K., Szabo, R., Wertz, P.W., Segre, J., Haudenschild, C.C., Kim, S.Y. and Bugge, T.H. (2003). Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. J Cell Biol 163, 901-10. [23] Benaud, C.M., Oberst, M., Dickson, R.B. and Lin, C.Y. (2002). Deregulated activation of matriptase in breast cancer cells. Clin Exp Metastasis 19, 639-49. [24] Tsai, W.C., Chu, C.H., Yu, C.P., Sheu, L.F., Chen, A., Chiang, H. and Jin, J.S. (2008). Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters. Dis Markers 24, 89-99. [25] Riddick, A.C. et al. (2005). Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 92, 2171-80. [26] Saleem, M. et al. (2006). A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1. Cancer Epidemiol Biomarkers Prev 15, 217-27. [27] Lee, J.W. et al. (2005). Increased expression of matriptase is associated with histopathologic grades of cervical neoplasia. Hum Pathol 36, 626-33. [28] Oberst, M.D. et al. (2002). Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters. Clin Cancer Res 8, 1101-7. [29] Lin, C.Y., Wang, J.K., Torri, J., Dou, L., Sang, Q.A. and Dickson, R.B. (1997). Characterization of a novel, membrane-bound, 80-kDa matrix-degrading protease from human breast cancer cells. Monoclonal antibody production, isolation, and localization. J Biol Chem 272, 9147-52. [30] Lin, C.Y., Anders, J., Johnson, M. and Dickson, R.B. (1999). Purification and characterization of a complex containing matriptase and a Kunitz-type serine protease inhibitor from human milk. J Biol Chem 274, 18237-42. [31] Shimomura, T. et al. (1997). Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor. J Biol Chem 272, 6370-6. [32] Laskowski, M., Jr. and Kato, I. (1980). Protein inhibitors of proteinases. Annu Rev Biochem 49, 593-626. [33] Shia, S. et al. (2005). Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J Mol Biol 346, 1335-49. [34] Fan, B., Wu, T.D., Li, W. and Kirchhofer, D. (2005). Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin. J Biol Chem 280, 34513-20. [35] Herter, S. et al. (2005). Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. Biochem J 390, 125-36. [36] Friedrich, R. et al. (2002). Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase. J Biol Chem 277, 2160-8. [37] Kojima, K., Tsuzuki, S., Fushiki, T. and Inouye, K. (2008). Roles of functional and structural domains of hepatocyte growth factor activator inhibitor type 1 in the inhibition of matriptase. J Biol Chem 283, 2478-87. [38] Oberst, M.D., Chen, L.Y., Kiyomiya, K., Williams, C.A., Lee, M.S., Johnson, M.D., Dickson, R.B. and Lin, C.Y. (2005). HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease. Am J Physiol Cell Physiol 289, C462-70. [39] Tanaka, H. et al. (2005). Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for branching morphogenesis in the chorioallantoic placenta. Mol Cell Biol 25, 5687-98. [40] Kang, J.Y., Dolled-Filhart, M., Ocal, I.T., Singh, B., Lin, C.Y., Dickson, R.B., Rimm, D.L. and Camp, R.L. (2003). Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer. Cancer Res 63, 1101-5. [41] Godiksen, S., Selzer-Plon, J., Pedersen, E.D., Abell, K., Rasmussen, H.B., Szabo, R., Bugge, T.H. and Vogel, L.K. (2008). Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary. Biochem J [42] Lin, C.Y., Tseng, I.C., Chou, F.P., Su, S.F., Chen, Y.W., Johnson, M.D. and Dickson, R.B. (2008). Zymogen activation, inhibition, and ectodomain shedding of matriptase. Front Biosci 13, 621-35. [43] List, K., Bugge, T.H. and Szabo, R. (2006). Matriptase: potent proteolysis on the cell surface. Mol Med 12, 1-7. [44] Kawaguchi, T., Qin, L., Shimomura, T., Kondo, J., Matsumoto, K., Denda, K. and Kitamura, N. (1997). Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor. J Biol Chem 272, 27558-64. [45] Marlor, C.W., Delaria, K.A., Davis, G., Muller, D.K., Greve, J.M. and Tamburini, P.P. (1997). Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains. J Biol Chem 272, 12202-8. [46] Muller-Pillasch, F., Wallrapp, C., Bartels, K., Varga, G., Friess, H., Buchler, M., Adler, G. and Gress, T.M. (1998). Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer. Biochim Biophys Acta 1395, 88-95. [47] Qin, L., Denda, K., Shimomura, T., Kawaguchi, T. and Kitamura, N. (1998). Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2. FEBS Lett 436, 111-4. [48] Delaria, K.A., Muller, D.K., Marlor, C.W., Brown, J.E., Das, R.C., Roczniak, S.O. and Tamburini, P.P. (1997). Characterization of placental bikunin, a novel human serine protease inhibitor. J Biol Chem 272, 12209-14. [49] Miyazawa, K., Shimomura, T., Kitamura, A., Kondo, J., Morimoto, Y. and Kitamura, N. (1993). 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 268, 10024-8. [50] Shimomura, T., Kondo, J., Ochiai, M., Naka, D., Miyazawa, K., Morimoto, Y. and Kitamura, N. (1993). Activation of the zymogen of hepatocyte growth factor activator by thrombin. J Biol Chem 268, 22927-32. [51] Miyazawa, K., Shimomura, T., Naka, D. and Kitamura, N. (1994). Proteolytic activation of hepatocyte growth factor in response to tissue injury. J Biol Chem 269, 8966-70. [52] Miyazawa, K., Shimomura, T. and Kitamura, N. (1996). Activation of hepatocyte growth factor in the injured tissues is mediated by hepatocyte growth factor activator. J Biol Chem 271, 3615-8. [53] Stoker, M., Gherardi, E., Perryman, M. and Gray, J. (1987). Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 327, 239-42. [54] Nakamura, T., Nawa, K., Ichihara, A., Kaise, N. and Nishino, T. (1987). Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett 224, 311-6. [55] Gohda, E. et al. (1988). Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest 81, 414-9. [56] Boros, P. and Miller, C.M. (1995). Hepatocyte growth factor: a multifunctional cytokine. Lancet 345, 293-5. [57] Matsumoto, K. and Nakamura, T. (1996). Emerging multipotent aspects of hepatocyte growth factor. J Biochem 119, 591-600. [58] Hamasuna, R., Kataoka, H., Meng, J.Y., Itoh, H., Moriyama, T., Wakisaka, S. and Koono, M. (2001). 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 93, 339-45. [59] Generali, D. et al. (2007). Regulation of hepatocyte growth factor activator inhibitor 2 by hypoxia in breast cancer. Clin Cancer Res 13, 550-8. [60] Fukai, K., Yokosuka, O., Chiba, T., Hirasawa, Y., Tada, M., Imazeki, F., Kataoka, H. and Saisho, H. (2003). Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma. Cancer Res 63, 8674-9. [61] Kataoka, H., Suganuma, T., Shimomura, T., Itoh, H., Kitamura, N., Nabeshima, K. and Koono, M. (1999). Distribution of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in human tissues. Cellular surface localization of HAI-1 in simple columnar epithelium and its modulated expression in injured and regenerative tissues. J Histochem Cytochem 47, 673-82. [62] Morris, M.R. et al. (2005). 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 65, 4598-606. [63] Yagyu, T., Kobayashi, H., Matsuzaki, H., Wakahara, K., Kondo, T., Kurita, N., Sekino, H. and Inagaki, K. (2006). Enhanced spontaneous metastasis in bikunin-deficient mice. Int J Cancer 118, 2322-8. [64] Kobayashi, H., Shinohara, H., Fujie, M., Gotoh, J., Itoh, M., Takeuchi, K. and Terao, T. (1995). Inhibition of metastasis of Lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models. Int J Cancer 63, 455-62. [65] Kobayashi, H., Gotoh, J., Kanayama, N., Hirashima, Y., Terao, T. and Sugino, D. (1995). Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition. Cancer Res 55, 1847-52. [66] Wakahara, K. et al. (2005). Bikunin suppresses lipopolysaccharide-induced lethality through down-regulation of tumor necrosis factor- alpha and interleukin-1 beta in macrophages. J Infect Dis 191, 930-8. [67] Tu, W.C., Wang, S.Y., Chien, S.C., Lin, F.M., Chen, L.R., Chiu, C.Y. and Hsiao, P.W. (2007). Diterpenes from Cryptomeria japonica inhibit androgen receptor transcriptional activity in prostate cancer cells. Planta Med 73, 1407-9. [68] Moriyama, T., Kataoka, H., Koono, M. and Wakisaka, S. (1999). Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review). Int J Mol Med 3, 531-6. [69] Schuster, J.M., Longo, M. and Nelson, P.S. (2003). Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment. J Neurooncol 64, 219-25. [70] Kobayashi, H. et al. (1998). A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and domain II of bikunin efficiently inhibits tumor cell invasion and metastasis. Eur J Biochem 253, 817-26. [71] Kobayashi, H., Shinohara, H., Gotoh, J., Fujie, M., Fujishiro, S. and Terao, T. (1995). Anti-metastatic therapy by urinary trypsin inhibitor in combination with an anti-cancer agent. Br J Cancer 72, 1131-7. [72] Parr, C. and Jiang, W.G. (2006). Hepatocyte growth factor activation inhibitors (HAI-1 and HAI-2) regulate HGF-induced invasion of human breast cancer cells. Int J Cancer 119, 1176-83. [73] Kataoka, H., Shimomura, T., Kawaguchi, T., Hamasuna, R., Itoh, H., Kitamura, N., Miyazawa, K. and Koono, M. (2000). Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment. J Biol Chem 275, 40453-62. [74] Syed, D.N., Afaq, F., Sarfaraz, S., Khan, N., Kedlaya, R., Setaluri, V. and Mukhtar, H. (2008). Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol [75] Itoh, H., Yamauchi, M., Kataoka, H., Hamasuna, R., Kitamura, N. and Koono, M. (2000). Genomic structure and chromosomal localization of the human hepatocyte growth factor activator inhibitor type 1 and 2 genes. Eur J Biochem 267, 3351-9. [76] Yagyu, T. et al. (2004). A kunitz-type protease inhibitor bikunin disrupts ligand-induced oligomerization of receptors for transforming growth factor (TGF)-beta and subsequently suppresses TGF-beta signalings. FEBS Lett 576, | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37625 | - |
dc.description.abstract | 第二型肝細胞生長因子活化抑制者(HAI-2)為一絲胺酸蛋白酶抑制者,具有抑制肝細胞生長活化子(HGFA)的活性。此外,HAI-2可有效降低神經膠質瘤細胞的轉移能力。在動物體實驗中也發現,相較於正常表現HAI-2的老鼠,HAI-2缺陷的老鼠在腹壁皮下注射肺癌細胞後,細胞轉移至肺部的機率較高。且研究發現HAI-2的表現量會隨著腫瘤發展過程逐漸減少。這些結果顯示HAI-2具有對抗癌細胞侵襲及轉移的特性。
因此,我們利用一套由中研院農業生技研究中心蕭培文博士建構出可模擬攝護腺癌惡化轉移的細胞模式,包括103E、N1以及N2細胞,來探討HAI-2在攝護腺癌發展過程中所扮演的角色。 我們發現,隨著103E、N1及N2細胞的轉移能力愈來愈強,HAI-2基因在細胞中的表現逐漸降低。另外,過量表現HAI-2可抑制N2細胞的侵襲能力(invasion),但卻可增加由肝細胞生長因子(HGF)所調控的細胞遷移能力(migration)。而這個 受到肝細胞生長因子所調控的遷移現象可能與間質蛋白酶(matriptase)相關。我們的研究結果顯示,HAI-2會經由其第一個Kuniz domain抑制間質蛋白酶的活化,而降低間質蛋白酶與其抑制者HAI-1所形成的130 kDa複合物,並使得另一70 kDa複合物的生成增加。HAI-2也會穩定原態間質蛋白酶的生成。經由免疫螢光染色分析,雖然HAI-2與間質蛋白酶共同聚集,但進一步利用免疫沉澱法後,卻發現HAI-2與間質蛋白酶之間沒有直接的交互作用。 综合以上結果,我們認為,HAI-2在人類攝護腺癌細胞的侵襲轉移以及間質蛋白酶的活化上扮演抑制的角色,但可提升細胞遷移能力。 | zh_TW |
dc.description.abstract | HAI-2 (Hepatocyte Growth Factor Activator Inhibitor-2) was identified as a serine protease inhibitor, showing a potent inhibition on HGFA (Hepatocyte Growth Factor Activator) activity. HAI-2 has been proved to play anti-invasive and anti-metastatic roles in human glioma. The expression level of HAI-2 is inversely correlated with tumor progression in human glioma and breast cancer.
In the study, a set of prostate cancer cell lines 103E, N1, and N2 cells with an increasing metastasis potential in mice, was established and kindly provided by Dr. Pei-Wen Hsiao, Agriculture Biotechnology Research Center, Academia Sinica. This model was used to examine whether HAI-2 also plays a role in the progression of human prostate cancer cells. We found that gene expression level of HAI-2 was inversely related to the increasing metastatic ability in 103E, N1, and N2 cells. Moreover, HAI-2 was shown to inhibit N2 cells invasion in vitro, but to promote cell migration in a HGF-mediated manner. In addition, the Kunitz domain I of HAI-2 plays an important role in enhancement of prostate cancer cell migration. We hypothesized that the involvement of HAI-2 in HGF-mediated motility is related to matriptase. Our data indicated that HAI-2 inhibited matriptase activation accompanied with a reduced formation of 130 kDa, activated matriptase/HAI-1 complex. HAI-2 also increased a formation of 70 kDa matriptase/HAI-1 complex. Furthermore, HAI-2 was found to stabilize the expression of latent matriptase. Colocalization of HAI-2 and matriptase was observed in vesicle-like structures with an immunofluorescence assay, but CoIP showed that there was no direct interaction between HAI-2 and matriptase. The results taken together indicated that HAI-2 plays an inhibitory role in cancer cell invasion and matriptase activation while HAI-2 can promote cell migration of human prostate cancer cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:35:30Z (GMT). No. of bitstreams: 1 ntu-97-R95442014-1.pdf: 4360849 bytes, checksum: de2d22be4a1100de8f8e6732296627bb (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 口試委員會審定書...................................................................................................i
Acknowledgement..............................................................................................................ii Abstract in Chinese............................................................................................................iii Abstract in English.............................................................................................................iv Content................................................................................................................................I List of Figures...................................................................................................................III Abbreviations....................................................................................................................IV Preface............................................................................................................................... V Chapter 1 Introduction................................................................................................ 1 1.1 Matriptase.........................................................................................................2 1.2 HAI-1 (Hepatocyte Growth Factor Activator Inhibitor-1)...............................6 1.3 Interactions between Matriptase and HAI-1...................................................10 1.4 HAI-2 (Hepatocyte Growth Factor Activator Inhibitor-2)..............................12 1.5 Research Motivation and Purpose...................................................................15 Chapter 2 Materials and Methods..............................................................................16 2.1 Materials..........................................................................................................17 2.2 Methods...........................................................................................................20 Chapter 3 Results..........................................................................................................28 3.1 The established prostate cancer xenograft model............................................29 3.2 Endogenous expression level of HAI-2 mRNA in 103E, N1, and N2 cells....30 3.3 Differential effects of HAI-2 on cell invasion and migration………….........30 3.4 HAI-2 cDNA cloning and construction of HAI-2 variants in a mammalian expression vector…………………………………………………….............31 3.5 HAI-2 enhances cell motility…………………………………………….....31 3.6 HAI-2 inhibits matriptase activation.............................................................32 3.7 HAI-2 stabilizes the expression of full length matriptase.............................35 3.8 HAI-2 increases a 70 kDa, activated matriptase/HAI-1 complex.................35 3.9 HAI-2 increases the ectodomain shedding of matriptase..............................36 3.10 Kunitz domain I is responsible for matriptase inhibition..............................36 3.11 Colocalization of HAI-2 and matriptase........................................................37 3.12 No direct interactions between HAI-2 and matriptase..................................38 Chapter 4 Discussion..................................................................................................39 4.1 Endogenous expression of HAI-2.................................................................40 4.2 Effects of HAI-2 on invasion and migration................................................40 4.3 Interactions between HAI-2 and matriptase.................................................42 4.4 Colocalization of HAI-2 and matriptase.......................................................44 Chapter 5 Figures.......................................................................................................46 Chapter 6 Appendix...................................................................................................61 Chapter 7 References.................................................................................................66 | |
dc.language.iso | en | |
dc.title | 第二型肝細胞生長因子活化抑制者在攝護腺癌細胞移動侵襲與調控間質蛋白酶活性的角色 | zh_TW |
dc.title | The roles of hepatocyte growth factor activator inhibitor-2 in prostate cancer cell migration, invasion and regulating matriptase activity | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林榮耀(Jung-Yaw Lin),呂紹俊(Shao-Chun Lu),游偉絢(Wei-Hsuan Yu),蕭培文(Pei-Wen Hsiao) | |
dc.subject.keyword | 第二型肝細胞生長因子活化抑制者,肝細胞生長因子,攝護腺癌,轉移,侵襲,間質蛋白酶, | zh_TW |
dc.subject.keyword | HAI-2,HGF,prostate cancer,migration,invasion,matriptase, | en |
dc.relation.page | 76 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-11 | |
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 |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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