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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李明學 | |
| dc.contributor.author | Cheng-Chung Huang | en |
| dc.contributor.author | 黃正忠 | zh_TW |
| dc.date.accessioned | 2021-05-20T19:58:32Z | - |
| dc.date.available | 2015-09-09 | |
| dc.date.available | 2021-05-20T19:58:32Z | - |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-15 | |
| dc.identifier.citation | 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.
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J Biol Chem 2002;277:10539-46. 32. Hung RJ, Hsu Ia W, Dreiling JL, Lee MJ, Williams CA, Oberst MD, Dickson RB, Lin CY. Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts. Am J Physiol Cell Physiol 2004;286:C1159-69. 33. Kiyomiya K, Lee MS, Tseng IC, Zuo H, Barndt RJ, Johnson MD, Dickson RB, Lin CY. 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 2006;291:C40-9. 34. Yu JX, Chao L, Chao J. Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA. J Biol Chem 1995;270:13483-9. 35. Chen LM, Hodge GB, Guarda LA, Welch JL, Greenberg NM, Chai KX. Down-regulation of prostasin serine protease: a potential invasion suppressor in prostate cancer. Prostate 2001;48:93-103. 36. Chen LM, Chai KX. Prostasin serine protease inhibits breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation. Int J Cancer 2002;97:323-9. 37. Chen LM, Wang C, Chen M, Marcello MR, Chao J, Chao L, Chai KX. Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation. Am J Physiol Renal Physiol 2006;291:F567-77. 38. Bruns JB, Carattino MD, Sheng S, Maarouf AB, Weisz OA, Pilewski JM, Hughey RP, Kleyman TR. Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit. J Biol Chem 2007;282:6153-60. 39. Carpenter G. Properties of the receptor for epidermal growth factor. Cell 1984;37:357-8. 40. Schlessinger J. The epidermal growth factor receptor as a multifunctional allosteric protein. Biochemistry 1988;27:3119-23. 41. Lee MS, Igawa T, Yuan TC, Zhang XQ, Lin FF, Lin MF. ErbB-2 signaling is involved in regulating PSA secretion in androgen-independent human prostate cancer LNCaP C-81 cells. Oncogene 2003;22:781-96. 42. Raymond E, Faivre S, Armand JP. Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs 2000;60 Suppl 1:15-23; discussion 41-2. 43. Wells A. EGF receptor. Int J Biochem Cell Biol 1999;31:637-43. 44. Ahmed SM, Salgia R. Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer. Respirology 2006;11:687-92. 45. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006;366:2-16. 46. Marks RA, Zhang S, Montironi R, McCarthy RP, MacLennan GT, Lopez-Beltran A, Jiang Z, Zhou H, Zheng S, Davidson DD, Baldridge LA, Cheng L. Epidermal growth factor receptor (EGFR) expression in prostatic adenocarcinoma after hormonal therapy: a fluorescence in situ hybridization and immunohistochemical analysis. Prostate 2008;68:919-23. 47. Gregory CW, Fei X, Ponguta LA, He B, Bill HM, French FS, Wilson EM. Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer. J Biol Chem 2004;279:7119-30. 48. Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, Papsidero L, Kim U, Chai LS, Kakati S, Arya SK, Sandberg AA. The LNCaP cell line--a new model for studies on human prostatic carcinoma. Prog Clin Biol Res 1980;37:115-32. 49. Igawa T, Lin FF, Lee MS, Karan D, Batra SK, Lin MF. Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model. Prostate 2002;50:222-35. 50. Lin MF, Lee MS, Zhou XW, Andressen JC, Meng TC, Johansson SL, West WW, Taylor RJ, Anderson JR, Lin FF. Decreased expression of cellular prostatic acid phosphatase increases tumorigenicity of human prostate cancer cells. J Urol 2001;166:1943-50. 51. Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF. Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 1978;21:274-81. 52. Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP. LNCaP model of human prostatic carcinoma. Cancer Res 1983;43:1809-18. 53. Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 1979;17:16-23. 54. Jacquinet E, Rao NV, Rao GV, Zhengming W, Albertine KH, Hoidal JR. Cloning and characterization of the cDNA and gene for human epitheliasin. Eur J Biochem 2001;268:2687-99. 55. Zhu ML, Kyprianou N. Role of androgens and the androgen receptor in epithelial-mesenchymal transition and invasion of prostate cancer cells. FASEB J 2010;24:769-77. 56. 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J Mater Sci Mater Med 2001;12:971-7. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8569 | - |
| dc.description.abstract | 攝護腺癌是西方男性最常發生的癌症之一。在台灣，因為生活飲食習慣逐漸地西化，攝護腺癌有逐年上升的趨勢，其死亡率在癌症死亡中排名第七位。目前對於人類攝護腺癌在轉變成為較惡化或具高度轉移的分子機制，尚未十分明瞭。近年來，有相關報告提出細胞表層蛋白分解反應的失調被認為與癌症的侵襲及轉移有直接的相關性。
因此，在本篇研究中，我們想探討可受雄性荷爾蒙調控的嵌膜絲胺酸蛋白酶:第二型膜上絲胺酸蛋白酶II (TMPRSS2)，在攝護腺癌細胞演進過程中所扮演的角色。首先我們將可表現此蛋白酶膜外區域的DNA片段建構在一個帶有組胺酸標記的哺乳動物分泌載體內，利用HEK293T細胞株進行蛋白表達並純化此蛋白做為抗原，以製作抗體。與林陳鏞博士合作下，我們成功地獲得一株可專一辨認第二型膜上絲胺酸蛋白酶II的單株抗體。在三株雄性荷爾蒙非依賴型細胞株 (DU145、PC-3 及 LNCaP C-81) 及一株雄性荷爾蒙依賴型細胞株LNCaP C-33中，第二型膜上絲胺酸蛋白酶II主要表現在荷爾蒙依賴型的細胞，其表現量會隨著細胞對雄性賀爾蒙非依賴的程度及高度侵襲能力的上升而下降。當使用核糖核酸干擾技術專一地將第二型膜上絲胺酸蛋白酶II的表現抑制時，會提升細胞生長的能力，但卻會使雄性荷爾蒙接收體以及攝護腺特異性抗原 (PSA) 的表現量減低。同時，我們也發現第二型膜上絲胺酸蛋白酶II對雄性荷爾蒙所調控的間質蛋白酶 (matriptase) 活化、攝護腺特異抗原的產生以及攝護腺癌細胞的生長，都扮演著重要的角色。另一方面，在攝護腺癌細胞演進的過程中，當第二型膜上絲胺酸蛋白酶II表現受到抑制時，會促使上皮細胞生長因子接受體表現上升，進而增強細胞對上皮細胞生長因子的敏感性，易於反應生長刺激。總歸上述，本篇研究結果顯示當減少或失去第二型膜上絲胺酸蛋白酶II的表現時，會促進細胞生長以及對上皮細胞生長因子的敏感度，進而在攝護腺癌細胞演進的過程中扮演一個重要的角色。 關鍵詞: 第二型膜上絲胺酸蛋白酶II；攝護腺癌；雄性荷爾蒙接受體；上皮細胞生長因子接受體；間質蛋白酶；前列腺蛋白酶。 | zh_TW |
| dc.description.abstract | Prostate cancer is one of the most common cancers among men in the western countries. In Taiwan, the incidence of prostate cancer has been rising to the seventh leading cause of cancer-related death, partly due to westernized life style and diets. Human prostate cancer usually undergoes several alterations to progress to advanced stages with androgen-independence and/or high metastasis. The molecular mechanisms for the progression are still not well understood. Recently, it has been proposed that deregulation of cell surface proteolysis is strongly involved in cancer cell invasion and metastasis.
In this study, we are interested in addressing the role of an androgen-regulated, membrane-anchored serine protease TMPRSS2 in the progression of prostate cancer cells, since a decreased expression of TMPRSS2 was shown in advanced prostate cancer. To explore the role of TMPRSS2 in prostate cancer, a monoclonal antibody (AL-20) against the protease was successfully generated by constructing the cDNA fragment encoding the extracellular region of TMPRSS2 inserted into a mammalian secretory vector with a His tag and purifying the fusion proteins as an antigen. With three androgen-independent prostate cancer cells (DU145, PC-3 and LNCaP C-81 cells) and an androgen-sensitive LNCaP C-33 cell, our data showed that the protein levels of TMPRSS2 were decreased in those cells with androgen-independence and highly invasive potentials. Moreover, a reduction of TMPRSS2 expression by shRNA approaches increased prostate cancer cell proliferation, but decreased the expression of androgen receptor (AR) and prostate-specific antigen (PSA). Furthermore, our data showed that TMPRSS2 was important for Dihydrotestosterone (DHT) -induced matriptase activation, PSA production and prostate cancer cell growth. On the other hand, down regulation of TMPRSS2 during the progression of prostate cancer cells decreased matriptase activation and increased the protein level of EGFR, leading to enhancement of EGF sensitivity for growth stimulation. Taken together, this study indicates that a decrease/loss of TMPRSS2 expression may play a role in the progression of prostate cancer cells, at least in part via increasing cell growth and EGF sensitivity. Key words: TMPRSS2; prostate cancer; androgen receptor; EGFR; matriptase; prostasin. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T19:58:32Z (GMT). No. of bitstreams: 1 ntu-99-R97442008-1.pdf: 1706494 bytes, checksum: e9066c0e8e4ef22469d58d52666b657b (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 中文摘要 i
ABSTRACT iii Chapter 1 Introduction 1 1.2 Type II transmembrane serine protease. 3 1.3 Type II transmembrane protease, serine 2 (TMPRSS2) 3 1.4 Matriptase 5 1.5 Prostasin (PRSS8) 7 1.6 Epidermal growth factor receptor (EGFR) 7 1.7 The purpose for this study 8 Chapter 2 Material & Methods 10 2.1 Materials 11 2.2. Methods 15 Chapter 3 Results 23 3.1 To generate a TMPRSS2 monoclonal antibody and detect the expression of TMPRSS2 in human prostate cancer cells. 24 3.2 Cell migration and invasion of different human prostate cancer LNCaP cells and the expression levels of TMPRSS2 in these two cells. 25 3.3 Role of TMPRSS2 in prostate cancer cell growth. 26 3.4 Effect of TMPRSS2 knockdown on prostate cancer cell migration. 27 3.5 Effect of DHT on TMPRSS2 expression. 28 3.6 Role of TMPRSS2 in AR transcriptional activity and protein stability. 29 3.7 Role of TMPRSS2 in DHT-induced prostate cancer cell growth. 30 3.8 Role of TMPRSS2 in activation of matriptase and matriptase/prostasin cascade. 31 3.9 Effect of TMPRSS2 knockdown on EGFR in prostate cancer cells. 32 3.10 Role of TMPRSS2 as a mediator between the signal pathways of androgens and EGF in prostate cancer cells. 33 Chapter 4 Discussion 35 4.1 TMPRSS2 in androgen sensitivity and cell migration. 36 4.2 TMPRSS2 in androgens-induced matriptase activation and EGFR processing. 37 4.3 TMPRSS2 in the EGF sensitivity of prostate cancer cells and in the cancer progression. 39 4.4 TMPRSS2 as a mediator between androgen signaling and EGFR pathway. 40 Chapter 5 Figures 42 Chapter 6 References 59 | |
| dc.language.iso | en | |
| dc.title | 第二型膜上絲胺酸蛋白酶II在攝護腺癌細胞扮演的角色 | zh_TW |
| dc.title | Role of TMPRSS2 in the progression of prostate cancer cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林榮耀,張震東,柯逢春,黃娟娟 | |
| dc.subject.keyword | 第二型膜上絲胺酸蛋白酶,II,攝護腺癌,雄性荷爾蒙接受體,上皮細胞生長因子接受體,間質蛋白酶,前列腺蛋白酶, | zh_TW |
| dc.subject.keyword | TMPRSS2,prostate cancer,androgen receptor,EGFR,matriptase,prostasin, | en |
| dc.relation.page | 65 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2010-07-15 | |
| 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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