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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 醫學檢驗暨生物技術學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80516
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dc.contributor.advisor林淑華(Shu-Wha Lin)
dc.contributor.authorChen-Hsiang Yangen
dc.contributor.author楊振翔zh_TW
dc.date.accessioned2022-11-24T03:08:21Z-
dc.date.available2021-11-03
dc.date.available2022-11-24T03:08:21Z-
dc.date.copyright2021-11-03
dc.date.issued2021
dc.date.submitted2021-10-27
dc.identifier.citation1.Leytus SP, Loeb KR, Hagen FS, Kurachi K Davie EW (1988) A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. Biochemistry 27, 1067-1074. 2.Tsuji A, Torres-Rosado A, Arai T, Le Beau MM, Lemons RS, Chou SH Kurachi K (1991) Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. J Biol Chem 266, 16948-16953. 3.Wu, Q. (2001). Gene targeting in hemostasis. Hepsin. Front Biosci. 6, D192-200. 4.Hooper, J.D., Campagnolo, L., Goodarzi, G., Truong, T.N., Stuhlmann, H., Quigley, J.P. (2003). Mouse matriptase-2: identification, characterization and comparative mRNA expression analysis with mouse hepsin in adult and embryonic tissues. Biochem. J. 373, 689-702. 5.Hooper JD, Clements JA, Quigley JP Antalis TM (2001) Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J Biol Chem 276, 857-860. 6.Barré O, Dufour A, Eckhard U, Kappelhoff R, Béliveau F, Leduc R Overall CM (2014) Cleavage specificity analysis of six type II transmembrane serine proteases (TTSPs) using PICS with proteome-derived peptide libraries. PLoS One 9, e105984. 7.Huber R Bode W (1978) Structural basis of the activation and action of trypsin. Acc Chem Res 11, 114-121. 8.Moran, P., Li, W., Fan, B., Vij, R., Eigenbrot, C., Kirchhofer, D. (2006). Pro-urokinase-type plasminogen activator is a substrate for hepsin. J. Biol. Chem. 281, 30439 -30446. 9.Chen, M., Chen, L.M., Lin, C.Y., Chai, K.X. (2010). Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor. Mol. Cell Biochem. 337, 259-266. 10.Wu, Q. (2001). Gene targeting in hemostasis. Hepsin. Front Biosci. 6, D192-200. 11.Halabian, R., Roudkenar, M.H., Esmaeili, N.S., Masroori, N., Roushandeh, A.M., Najafabadi, A.J. (2009). Establishment of a cell line expressing recombinant factor VII and its subsequent conversion to active form FVIIa through hepsin by genetic engineering method. Vox Sang 96, 309-315. 12.Herter, S., Piper, D.E., Aaron, W., Gabriele, T., Cutler, G., Cao, P., Bhatt, A.S., Choe, Y., Craik, C.S., Walker, N., Meininger, D., Hoey, T., Austin, R.J. (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, 125-136. 13.Owen, K.A., Qiu, D., Alves, J., Schumacher, A.M., Kilpatrick, L.M., Li, J., Harris, J.L., Ellis, V. (2010). Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA. Biochem. J. 426, 219-228. 14.Tripathi, M., Nandana, S., Yamashita, H., Ganesan, R., Kirchhofer, D., Quaranta, V. (2008). Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression. J. Biol.Chem. 283, 30576-30584. 15.Li S, Peng J, Wang H, Zhang W, Brown JM, Zhou Y Wu Q (2020) Hepsin enhances liver metabolism and inhibits adipocyte browning in mice. Proc Natl Acad Sci USA 117, 12359-12367. 16.Brunati M, Perucca S, Han L, Cattaneo A, Consolato F, Andolfo A, Schaeffer C, Olinger E, Peng J, Santambrogio S et al. (2015) The serine protease hepsin mediates urinary secretion and polymerization of Zona Pellucida domain protein uromodulin. eLife 4, e08887. 17.Olinger E, Lake J, Sheehan S, Schiano G, Takata T, Tokonami N, Debaix H, Consolato F, Rampoldi L, Korstanje R et al. (2019) Hepsin-mediated processing of uromodulin is crucial for salt-sensitivity and thick ascending limb homeostasis. Sci Rep 9, 12287. 18.Guipponi M, Antonarakis SE Scott HS (2008) TMPRSS3, a type II transmembrane serine protease mutated in non-syndromic autosomal recessive deafness. Front Biosci 13, 1557-1567. 19.Martin CE List K (2019) Cell surface-anchored serine proteases in cancer progression and metastasis. Cancer Metastasis Rev 38, 357-387. 20.Mukai S, Yamasaki K, Fujii M, Nagai T, Terada N, Kataoka H Kamoto T (2020) Dysregulation of type II transmembrane serine proteases and ligand-dependent activation of MET in urological cancers. Int J Mol Sci 21, 2663. 21.Tanabe LM List K (2017) The role of type II transmembrane serine protease-mediated signaling in cancer. FEBS J 284, 1421-1436. 22.Wu Q Parry G (2007) Hepsin and prostate cancer. Front Biosci 12, 5052-5059. 23.Magee JA, Araki T, Patil S, Ehrig T, True L, Humphrey PA, Catalona WJ, Watson MA Milbrandt J (2001) Expression profiling reveals hepsin overexpression in prostate cancer. Cancer Res 61, 5692-5696. 24.Klezovitch O, Chevillet J, Mirosevich J, Roberts RL, Matusik RJ Vasioukhin V (2004) Hepsin promotes prostate cancer progression and metastasis. Cancer Cell 6, 185-195. 25.Valkenburg KC, Hostetter G Williams BO (2015) Concurrent Hepsin overexpression and adenomatous polyposis coli deletion causes invasive prostate carcinoma in mice. Prostate 75, 1579-1585. 26.Tang X, Mahajan SS, Nguyen LT, Béliveau F, Leduc R, Simon JA Vasioukhin V (2014) Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis. Oncotarget 5, 1352-1362. 27.John Beard, Sam Eddington, Noah Bowman, Adam Cole, Timothy O'Brien and Blake P. Johnson (2020) Abstract 6450: Circulating hepsin as a novel serum biomarker in prostate cancer patients. Cancer Res 80, 6450 28.Zhukov A, Hellman U Ingelman-Sundberg M (1997) Purification and characterization of hepsin from rat liver microsomes. Biochim Biophys Acta 1337, 85-95. 29.Vu TK, Liu RW, Haaksma CJ, Tomasek JJ Howard EW (1997) Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos. J Biol Chem 272, 31315-31320. 30.Wang L, Zhang C, Sun S, Chen Y, Hu Y, Wang H, Liu M, Dong N Wu Q (2019) Autoactivation and calpain-1-mediated shedding of hepsin in human hepatoma cells. Biochem J 476, 2355-2369. 31.Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3) Invest Urol. 17:16–23.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80516-
dc.description.abstractHepsin為第二型穿膜絲胺酸蛋白酶,主要表現於肝臟。Hepsin可以促進肝細胞中肝醣、脂質和蛋白質的生合成與白色脂肪組織的棕化,參與在尿調理素的聚合作用,以及與耳蝸發育相關。在前列腺癌中,Hepsin的表現量有顯著上升,且過表現Hepsin會促進腫瘤的侵入及轉移,而抑制Hepsin的表現則能降低前列腺癌轉移至骨頭、肝臟與肺臟。另外,循環系統中的Hepsin亦有被作為前列腺癌的生物指標之一,顯示游離型(soluble form) Hepsin之重要性。游離型Hepsin即是由細胞膜上的Hepsin經自體催化(autocatalysis)的方式活化後,所釋放出的包含絲胺酸酵素的細胞外區域。本篇論文欲建構穩定表現游離型Hepsin蛋白質的小鼠模型,探討在高表現游離型Hepsin對前列腺癌細胞在肺臟所造成的影響。我們首先以細胞株大量表現游離型Hepsin蛋白質,再進行蛋白質純化。先後使用腹腔注射方式及埋入式滲透壓幫浦,均無法在小鼠體內穩定表現游離型Hepsin。接著,我們以皮下注射方式將表現游離型Hepsin蛋白質的細胞株植入小鼠體內,成功在小鼠血液中測得大量游離型Hepsin。進一步在小鼠的左肺植入前列腺細胞株PC3細胞進行觀察,結果顯示雖未達統計意義,游離型Hepsin似乎可促進PC3細胞在小鼠肺臟的生長。zh_TW
dc.description.provenanceMade available in DSpace on 2022-11-24T03:08:21Z (GMT). No. of bitstreams: 1
U0001-2710202102301300.pdf: 3372298 bytes, checksum: fd0ce98661d0b491a2df4ee2cf7e3096 (MD5)
Previous issue date: 2021
en
dc.description.tableofcontents口試委員審定書………………………………………………I 致謝……………………………………………………………………II 中文摘要…………………………………………………………III 英文摘要…………………………………………………………IV 總目錄…………………………………………………………………V 圖目錄………………………………………………………………VI 表目錄………………………………………………………………VII 第一章 緒論………………………………………………………1 第二章 實驗材料與方法………………………………5 第三章 實驗結果……………………………………………13 第四章 討論………………………………………………………17 參考文獻………………………………………………………………20 圖……………………………………………………………………....23 附表…………………………………………………………………………37 附錄…………………………………………………………………………39
dc.language.isozh-TW
dc.subject小鼠模型zh_TW
dc.subject游離型Hepsinzh_TW
dc.subject蛋白質純化zh_TW
dc.subject前列腺癌zh_TW
dc.subject肺臟zh_TW
dc.subjectprostate canceren
dc.subjectmouse modelen
dc.subjectlungen
dc.subjectsoluble form hepsinen
dc.subjectprotein purificationen
dc.title探討游離型Hepsin對前列腺癌細胞在小鼠肺臟的影響zh_TW
dc.titleThe Effect of Soluble Hepsin on Prostate Cancer Cells in The Lungs of Miceen
dc.date.schoolyear109-2
dc.description.degree碩士
dc.contributor.oralexamcommittee吳瑞菁(Hsin-Tsai Liu),黃祥博(Chih-Yang Tseng),游益興
dc.subject.keyword游離型Hepsin,蛋白質純化,前列腺癌,肺臟,小鼠模型,zh_TW
dc.subject.keywordsoluble form hepsin,protein purification,prostate cancer,lung,mouse model,en
dc.relation.page39
dc.identifier.doi10.6342/NTU202104290
dc.rights.note同意授權(限校園內公開)
dc.date.accepted2021-10-27
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept醫學檢驗暨生物技術學研究所zh_TW
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