請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63947完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李明學 | |
| dc.contributor.author | Hsin-Ying Lin | en |
| dc.contributor.author | 林心瀅 | zh_TW |
| dc.date.accessioned | 2021-06-16T17:24:02Z | - |
| dc.date.available | 2015-09-19 | |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-16 | |
| dc.identifier.citation | 1. WHO, 2011.
2. 中華民國行政院衛生署 2011. 3. Agarwal, R., Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents. Biochem Pharmacol, 2000. 60(8): p. 1051-9. 4. Saraon, P., K. Jarvi, and E.P. Diamandis, Molecular alterations during progression of prostate cancer to androgen independence. Clin Chem, 2011. 57(10): p. 1366-75. 5. Clarke, N.W., C.A. Hart, and M.D. Brown, Molecular mechanisms of metastasis in prostate cancer. Asian J Androl, 2009. 11(1): p. 57-67. 6. Nguyen, D.X., P.D. Bos, and J. Massague, Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer, 2009. 9(4): p. 274-84. 7. Joyce, J.A. and J.W. Pollard, Microenvironmental regulation of metastasis. Nat Rev Cancer, 2009. 9(4): p. 239-52. 8. Thiery, J.P., Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2002. 2(6): p. 442-54. 9. Huber, M.A., N. Kraut, and H. Beug, Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol, 2005. 17(5): p. 548-58. 10. Yingling, J.M., K.L. Blanchard, and J.S. Sawyer, Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov, 2004. 3(12): p. 1011-22. 11. Kessenbrock, K., V. Plaks, and Z. Werb, Matrix metalloproteinases: regulators of the tumor microenvironment. Cell, 2010. 141(1): p. 52-67. 12. Gomes, L.R., et al., TGF-beta1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer, 2012. 12: p. 26. 13. Mani, S.A., et al., The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008. 133(4): p. 704-15. 14. Ma, L., et al., Role of epidermal-growth-factor receptor in tumor progression in transformed human mammary epithelial cells. Int J Cancer, 1998. 78(1): p. 112-9. 15. Yarom, N., et al., EGFR expression variance in paired colorectal cancer primary and metastatic tumors. Cancer Biol Ther, 2010. 10(5): p. 416-21. 16. Kim, H.G., et al., EGF receptor signaling in prostate morphogenesis and tumorigenesis. Histol Histopathol, 1999. 14(4): p. 1175-82. 17. Seshacharyulu, P., et al., Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets, 2012. 16(1): p. 15-31. 18. Guo, X. and X.F. Wang, Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res, 2009. 19(1): p. 71-88. 19. Noel, A., et al., Membrane associated proteases and their inhibitors in tumour angiogenesis. J Clin Pathol, 2004. 57(6): p. 577-84. 20. Netzel-Arnett, S., et al., Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev, 2003. 22(2-3): p. 237-58. 21. Woessner, J.F., Jr., The family of matrix metalloproteinases. Ann N Y Acad Sci, 1994. 732: p. 11-21. 22. Snoek-van Beurden, P.A. and J.W. Von den Hoff, Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors. Biotechniques, 2005. 38(1): p. 73-83. 23. Gordon, K.J. and G.C. Blobe, Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta, 2008. 1782(4): p. 197-228. 24. Derynck, R. and Y.E. Zhang, Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003. 425(6958): p. 577-84. 25. Clark, D.A. and R. Coker, Transforming growth factor-beta (TGF-beta). Int J Biochem Cell Biol, 1998. 30(3): p. 293-8. 26. Zwaagstra, J.C., M. El-Alfy, and M.D. O'Connor-McCourt, Transforming growth factor (TGF)-beta 1 internalization: modulation by ligand interaction with TGF-beta receptors types I and II and a mechanism that is distinct from clathrin-mediated endocytosis. J Biol Chem, 2001. 276(29): p. 27237-45. 27. Xu, L., Regulation of Smad activities. Biochim Biophys Acta, 2006. 1759(11-12): p. 503-13. 28. Massague, J., J. Seoane, and D. Wotton, Smad transcription factors. Genes Dev, 2005. 19(23): p. 2783-810. 29. Massague, J., TGFbeta in Cancer. Cell, 2008. 134(2): p. 215-30. 30. Ikushima, H. and K. Miyazono, TGFbeta signalling: a complex web in cancer progression. Nat Rev Cancer, 2010. 10(6): p. 415-24. 31. Zhang, Y.E., Non-Smad pathways in TGF-beta signaling. Cell Res, 2009. 19(1): p. 128-39. 32. Shi, Y. and J. Massague, Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell, 2003. 113(6): p. 685-700. 33. Zhang, Y., et al., Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci U S A, 2001. 98(3): p. 974-9. 34. Zhu, H., et al., A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature, 1999. 400(6745): p. 687-93. 35. Lin, X., M. Liang, and X.H. Feng, Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem, 2000. 275(47): p. 36818-22. 36. Hayes, S., A. Chawla, and S. Corvera, TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol, 2002. 158(7): p. 1239-49. 37. Chen, Y.G., Endocytic regulation of TGF-beta signaling. Cell Res, 2009. 19(1): p. 58-70. 38. Matsuzaki, K., Smad phosphoisoform signaling specificity: the right place at the right time. Carcinogenesis, 2011. 32(11): p. 1578-88. 39. Kretzschmar, M., et al., A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev, 1999. 13(7): p. 804-16. 40. Pardali, K., et al., Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem, 2000. 275(38): p. 29244-56. 41. Chen, X., et al., Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature, 1997. 389(6646): p. 85-9. 42. Germain, S., et al., Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. Genes Dev, 2000. 14(4): p. 435-51. 43. Wong, C., et al., Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta. Mol Cell Biol, 1999. 19(3): p. 1821-30. 44. Feng, X.H., et al., Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B). Mol Cell, 2002. 9(1): p. 133-43. 45. Feng, X.H., et al., The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation. Genes Dev, 1998. 12(14): p. 2153-63. 46. Bai, R.Y., et al., SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling. Nat Cell Biol, 2002. 4(3): p. 181-90. 47. Kato, Y., et al., A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature, 2002. 418(6898): p. 641-6. 48. Luo, K., Ski and SnoN: negative regulators of TGF-beta signaling. Curr Opin Genet Dev, 2004. 14(1): p. 65-70. 49. Verschueren, K., et al., SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes. J Biol Chem, 1999. 274(29): p. 20489-98. 50. Kim, R.H., et al., A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction. Genes Dev, 2000. 14(13): p. 1605-16. 51. Wang, S.E., et al., Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol Cell Biol, 2008. 28(18): p. 5605-20. 52. Liu, T. and X.H. Feng, Regulation of TGF-beta signalling by protein phosphatases. Biochem J, 2010. 430(2): p. 191-8. 53. Lu, T., et al., Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways. Proc Natl Acad Sci U S A, 2007. 104(11): p. 4365-70. 54. Tang, B., et al., TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest, 2003. 112(7): p. 1116-24. 55. Wakefield, L.M. and A.B. Roberts, TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev, 2002. 12(1): p. 22-9. 56. Gorelik, L. and R.A. Flavell, Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity, 2000. 12(2): p. 171-81. 57. Letterio, J.J. and A.B. Roberts, Regulation of immune responses by TGF-beta. Annu Rev Immunol, 1998. 16: p. 137-61. 58. Scandura, J.M., et al., Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Proc Natl Acad Sci U S A, 2004. 101(42): p. 15231-6. 59. Krimpenfort, P., et al., p15Ink4b is a critical tumour suppressor in the absence of p16Ink4a. Nature, 2007. 448(7156): p. 943-6. 60. Chen, G., C. Deng, and Y.P. Li, TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci, 2012. 8(2): p. 272-88. 61. Slabakova, E., et al., TGF-beta1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Prostate, 2011. 71(12): p. 1332-43. 62. De Wever, O. and M. Mareel, Role of tissue stroma in cancer cell invasion. J Pathol, 2003. 200(4): p. 429-47. 63. Thomas, D.A. and J. Massague, TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 2005. 8(5): p. 369-80. 64. 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. 65. Cho, E.G., et al., N-terminal processing is essential for release of epithin, a mouse type II membrane serine protease. J Biol Chem, 2001. 276(48): p. 44581-9. 66. Tanimoto, H., et al., Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention. Tumour Biol, 2001. 22(2): p. 104-14. 67. Lin, C.Y., et al., Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. J Biol Chem, 1999. 274(26): p. 18231-6. 68. MS, L., Matrix-degrading Type II transmembrane serine protease matriptase: its role in cancer development and malignancy. Journal of Cancer Molecules, 2006. 5. 69. Kim, C., et al., Filamin is essential for shedding of the transmembrane serine protease, epithin. EMBO Rep, 2005. 6(11): p. 1045-51. 70. Cho, E.G., R.H. Schwartz, and M.G. Kim, Shedding of membrane epithin is blocked without LDLRA4 and its protease activation site. Biochem Biophys Res Commun, 2005. 327(1): p. 328-34. 71. Oberst MD, C.L., Kiyomiya K, Williams CA, Lee MS, Johnson MD, Dickson RB, Lin CY. , HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease. Am J Physiol Cell Physiol, 2005. 289: p. 8. 72. Benaud, C., R.B. Dickson, and C.Y. Lin, Regulation of the activity of matriptase on epithelial cell surfaces by a blood-derived factor. Eur J Biochem, 2001. 268(5): p. 1439-47. 73. Uhland, K., Matriptase and its putative role in cancer. Cell Mol Life Sci, 2006. 63(24): p. 2968-78. 74. Kiyomiya, K., et al., 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(1): p. C40-9. 75. Oberst, M.D., et al., 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, 2002. 8(4): p. 1101-7. 76. Riddick, A.C., et al., Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer, 2005. 92(12): p. 2171-80. 77. Saleem, M., et al., 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, 2006. 15(2): p. 217-27. 78. Kang, J.Y., et al., 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, 2003. 63(5): p. 1101-5. 79. Velasco, G., et al., Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins. J Biol Chem, 2002. 277(40): p. 37637-46. 80. Beliveau, F., A. Desilets, and R. Leduc, Probing the substrate specificities of matriptase, matriptase-2, hepsin and DESC1 with internally quenched fluorescent peptides. FEBS J, 2009. 276(8): p. 2213-26. 81. Stirnberg, M., et al., Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface. Biochem J, 2010. 430(1): p. 87-95. 82. Beliveau, F., et al., Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionality. J Biol Chem, 2011. 286(33): p. 29035-43. 83. Hentze, M.W., et al., Two to tango: regulation of Mammalian iron metabolism. Cell, 2010. 142(1): p. 24-38. 84. Nemeth, E., et al., Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 2004. 306(5704): p. 2090-3. 85. Folgueras, A.R., et al., Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood, 2008. 112(6): p. 2539-45. 86. Meynard, D., et al., Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood, 2011. 118(3): p. 747-56. 87. Babitt, J.L., et al., Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet, 2006. 38(5): p. 531-9. 88. Corradini, E., J.L. Babitt, and H.Y. Lin, The RGM/DRAGON family of BMP co-receptors. Cytokine Growth Factor Rev, 2009. 20(5-6): p. 389-98. 89. Silvestri, L., et al., The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab, 2008. 8(6): p. 502-11. 90. Finberg, K.E., et al., Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood, 2010. 115(18): p. 3817-26. 91. Finberg, K.E., et al., Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet, 2008. 40(5): p. 569-71. 92. Parr, C., et al., Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients. Clin Cancer Res, 2007. 13(12): p. 3568-76. 93. Sanders, A.J., et al., Genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation. J Cell Physiol, 2008. 216(3): p. 780-9. 94. Sanders, A.J., et al., The type II transmembrane serine protease, matriptase-2: Possible links to cancer? Anticancer Agents Med Chem, 2010. 10(1): p. 64-9. 95. Kaighn, M.E., et al., Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol, 1979. 17(1): p. 16-23. 96. Stone, K.R., et al., Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer, 1978. 21(3): p. 274-81. 97. Russell, P.J. and E.A. Kingsley, Human prostate cancer cell lines. Methods Mol Med, 2003. 81: p. 21-39. 98. Ramsay, A.J., et al., Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematologica, 2009. 94(6): p. 840-9. 99. Imamura, T., et al., Smad6 inhibits signalling by the TGF-beta superfamily. Nature, 1997. 389(6651): p. 622-6. 100. Bilandzic, M. and K.L. Stenvers, Betaglycan: a multifunctional accessory. Mol Cell Endocrinol, 2011. 339(1-2): p. 180-9. 101. Edwards, I.J., Proteoglycans in prostate cancer. Nat Rev Urol, 2012. 9(4): p. 196-206. 102. Hannon, G.J. and D. Beach, p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature, 1994. 371(6494): p. 257-61. 103. Datto, M.B., et al., Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci U S A, 1995. 92(12): p. 5545-9. 104. Yagi, K., et al., c-myc is a downstream target of the Smad pathway. J Biol Chem, 2002. 277(1): p. 854-61. 105. Lu, Z., et al., Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase. Mol Cell Biol, 2001. 21(12): p. 4016-31. 106. Vlahovic, G. and J. Crawford, Activation of tyrosine kinases in cancer. Oncologist, 2003. 8(6): p. 531-8. 107. Seiki, M. and I. Yana, Roles of pericellular proteolysis by membrane type-1 matrix metalloproteinase in cancer invasion and angiogenesis. Cancer Sci, 2003. 94(7): p. 569-74. 108. Wolf, K., et al., Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol, 2007. 9(8): p. 893-904 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63947 | - |
| dc.description.abstract | 癌症轉移是導致癌症病人預後不佳及死亡率上升的主要原因。第二型細胞間質蛋白酶[(Matriptase-2 (MTX2)]，隸屬於第二型穿膜絲胺酸蛋白酶家族(TTPSs)，與第一型細胞間質蛋白酶[(Matriptase (MTX)]具高度相似性。先前報導指出MTX2可能抑制癌症細胞功能，然而其詳細的機制仍然不清楚。為了進一步探討MTX2如何抑制攝護腺癌細胞的移動與侵襲能力，我大量表達Matriptase-2在攝護腺癌細胞中(PC3 和DU-145)，並發現此蛋白酶可明顯地降低攝護腺癌細胞的侵襲和移動能力。因先前報導指出上皮細胞轉形成間葉細胞的過程(epithelial mesenchymal transition (EMT))在癌症的轉移進程中扮演重要的角色。利用QRT-PCR得知，在表達MTX2之PC3細胞中，EMT相關的轉錄因子基因(Twist, SIP-1)表現量都下降，且 MMP9 (Matrix metallopeptidase 9)的基因和活化程度也隨之降低，這些結果顯示MTX2可藉由改變EMT來抑制攝護腺癌細胞的移動能力。轉化生長因子β（TGF-β）已被報導為強效性的EMT促進者。而利用西方點墨法發現典型的TGF-β訊息傳導下游的Smad2及Smad3之蛋白質量和磷酸化程度因MTX-2的表達而下降。此外，上皮生長因子受體(EGFR)的磷酸化程度也隨之下降，因此而探討MTX-2是否可影響其他膜上蛋白酶，進而降低癌細胞的侵襲力，由於先前研究指出MTX與攝護腺癌細胞的轉移有很大的關係，我也探討MTX2和MTX之間是否會影響。結果顯示在表達MTX2的PC3細胞，MTX的基因和蛋白質表現量都是明顯的下降。同時MTX2會促進MTX被分泌到細胞外。綜合以上結果，MTX2可藉由降低TGF-β訊息路徑下游分子之活化，抑制EGFR磷酸化以及MTX的表達，故MTX2扮演具抑制攝護腺癌細胞侵襲的角色。 | zh_TW |
| dc.description.abstract | Metastasis is often associated with a poor prognosis and isa leading cause of cancer mortality in prostate cancer. Matriptase-2 (MTX2) is a member of the type II transmembrane serine protease (TTSP) family and has a similar domain structure to matriptase which can enhance cancer cell invasion and migration. Some research results have indicated that MTX2 functions as a tumor suppressor. However, the molecular mechanisms by which MTX2 plays a negative role in prostate cancer are still unclear. In this study, examination the role of MTX2 in prostate cancer cell migration and invasion by ectopic expression of MTX2 in prostate cancer cells (PC3 and DU145). Data suggested that MTX2 reduced cell invasion and migration of PC3 and DU-145 cells. Moreover, MTX2 could down-regulate the mRNA levels of Twist, SIP-1, and the expression and gelatinolytic activity of MMP9, suggesting the involvement of MTX2 in altering an epithelial mesenchymal transition (EMT)-like event. Moreover, to further analyze if MTX2 was involved in modulating the TGF-β signaling pathway, a strong EMT inducer, we found that both protein and phosphorylation levels of TGF/BMP signaling effectors, Smad2 and Smad3, were decreased in MTX2-overexpressing cells. Furthermore, the ectopic expression of MTX2 also decreased the phosphorylation levels of epidermal growth factor receptor (EGFR), and was concurrent with a reduction of the gene and protein levels of matriptase, an oncogenic membrane-anchored serine protease in prostate cancer PC3 cells. Taken together, the data indicate that MTX2 functions as a suppressor of prostate cancer cell migration and invasion, at least in part via reducing the protein and phosphorylation levels of Smad2 and Smad3, the phosphorylation of EGFR, or the expression and activated levels of MTX. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T17:24:02Z (GMT). No. of bitstreams: 1 ntu-101-R99442009-1.pdf: 3852658 bytes, checksum: 84e0d28b079f23efe2a14a428e94d351 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 致謝 I
摘要 III Abstract IV Chapter 1.Introduction 1 1.1 Prostate cancer 2 1.2 Cancer metastasis 2 1.3. Transforming Growth Factor β (TGF-β) superfamily 4 1.3.1 The canonical pathway activated by Transforming Growth Factor β (TGF-β) superfamily 7 1.3.2 Non-canonical pathways induced by Transforming Growth Factor β (TGF-β) superfamily. 8 1.3.3 The TGF-β pathway in cancer cell 8 1.4 Matriptase 9 1.4.1 Matriptase processing 10 1.4.2 Matriptase and cancer cell progrssion 11 1.5 Matriptase 2 12 1.5.1 Matriptase-2 processing 13 1.5.2 Matriptase-2 function in hepatocyte: iron metabolism 13 1.5.3 Matriptase-2 and cancer progression 14 1.6 Research motivation 15 Chapter2. Materials and Methods 17 2.1 Materials 18 2.2 Methods 22 Chapter3. Results 35 3.1 Establishment of stable Matriptase-2-overexpressing PC3 and DU-145 cell pools 36 3.2 Matriptase-2 reduces the cell migration and invasion of PC3 and DU145 cells 37 3.3 Involvement of Matriptase-2 in altering the epithial mesenchymal transition (EMT)-Like phenotype of prostate cancer cells 37 3.4 MTX2 down-regulated TGF-β signal transductions in overexpression PC3 and DU145 cells 39 3.5 MTX2 down-regulated EGFR signaling in PC3 and DU-145 cells .40 3.6 Matriptase-2 can reduce the effect of TGF-β1 or EGF-induced PC3 cell invasion 40 3.7 Effects of MTX2 overexpression on the TGF-β, c-Met and EGFR signaling in HepG2 and CWR22Rv1 cells 41 3.8 Role of Matriptase-2 in the cell growth of PC3, DU145 and CWR22Rv1 cells 42 3.9 Matriptase-2 affects TGF-β receptors in PC3, HepG2 and CWR22Rv1 cells 43 3.10 Role of matriptase-2 in TGF-β-induced signaling in PC3 cells 43 3.11 Knockdown of MTX2 can up-regulate TGFβ/BMP signaling and E-cadherin protein level 45 3.12 MTX-2 can reduce the expression of Matriptase in prostate cancer cells 45 3.13 MTX2 can reduce the stimulatory effects of TGF-β1 and EGF on MTX gene expression in PC3 cell 47 Chapter 4. Discussion 49 Chapter 5. Figures 55 6. References 77 | |
| dc.language.iso | en | |
| dc.subject | 第二型細胞間質蛋白酶 | zh_TW |
| dc.subject | 癌症侵襲 | zh_TW |
| dc.subject | Matriptase-2 | en |
| dc.subject | TMPRSS6 | en |
| dc.subject | Invasion | en |
| dc.title | 探討第二型間質蛋白酶在人類攝護腺癌細胞轉移中所扮演的角色 | zh_TW |
| dc.title | Role of matriptase-2 in human prostate cancer migration and invasion. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林淑華,余明俊,張明富,陳青周 | |
| dc.subject.keyword | 第二型細胞間質蛋白酶,癌症侵襲, | zh_TW |
| dc.subject.keyword | Matriptase-2,TMPRSS6,Invasion, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-16 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 未授權公開取用 | 3.76 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。