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完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor李明亭
dc.contributor.authorHao-Hsiang Hungen
dc.contributor.author洪浩翔zh_TW
dc.date.accessioned2021-06-13T04:13:12Z-
dc.date.available2006-07-28
dc.date.copyright2006-07-28
dc.date.issued2006
dc.date.submitted2006-07-24
dc.identifier.citationAlbini, A., Y. Iwamoto, H.K. Kleinman, G.R. Martin, S.A. Aaronson, J.M. Kozlowski, and R.N. McEwan. 1987. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 47:3239-45.
Bae, Y.S., S.W. Kang, M.S. Seo, I.C. Baines, E. Tekle, P.B. Chock, and S.G. Rhee. 1997. Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J Biol Chem. 272:217-21.
Beauchamp, C., and I. Fridovich. 1971. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 44:276-87.
Behrend, L., G. Henderson, and R.M. Zwacka. 2003. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans. 31:1441-4.
Belien, A.T., P.A. Paganetti, and M.E. Schwab. 1999. Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter. J Cell Biol. 144:373-84.
Brenneisen, P., H. Sies, and K. Scharffetter-Kochanek. 2002. Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events. Ann N Y Acad Sci. 973:31-43.
Brigelius-Flohe, R., A. Banning, M. Kny, and G.F. Bol. 2004. Redox events in interleukin-1 signaling. Arch Biochem Biophys. 423:66-73.
Burdon, R.H. 1995. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med. 18:775-94.
Chiarugi, P., T. Fiaschi, M.L. Taddei, D. Talini, E. Giannoni, G. Raugei, and G. Ramponi. 2001. Two vicinal cysteines confer a peculiar redox regulation to low molecular weight protein tyrosine phosphatase in response to platelet-derived growth factor receptor stimulation. J Biol Chem. 276:33478-87.
Chiarugi, P., G. Pani, E. Giannoni, L. Taddei, R. Colavitti, G. Raugei, M. Symons, S. Borrello, T. Galeotti, and G. Ramponi. 2003. Reactive oxygen species as essential mediators of cell adhesion: the oxidative inhibition of a FAK tyrosine phosphatase is required for cell adhesion. J Cell Biol. 161:933-44.
Chin, J.R., G. Murphy, and Z. Werb. 1985. Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates. J Biol Chem. 260:12367-76.
Clark, E.A., T.R. Golub, E.S. Lander, and R.O. Hynes. 2000. Genomic analysis of metastasis reveals an essential role for RhoC. Nature. 406:532-5.
Clerch, L.B., D. Massaro, and A. Berkovich. 1998. Molecular mechanisms of antioxidant enzyme expression in lung during exposure to and recovery from hyperoxia. Am J Physiol. 274:L313-9.
Clerk, A., A. Michael, and P.H. Sugden. 1998. Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes. Biochem J. 333 ( Pt 3):581-9.
Colavitti, R., G. Pani, B. Bedogni, R. Anzevino, S. Borrello, J. Waltenberger, and T. Galeotti. 2002. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. J Biol Chem. 277:3101-8.
Deora, A.A., T. Win, B. Vanhaesebroeck, and H.M. Lander. 1998. A redox-triggered ras-effector interaction. Recruitment of phosphatidylinositol 3'-kinase to Ras by redox stress. J Biol Chem. 273:29923-8.
DiPersio, C.M., M. Shao, L. Di Costanzo, J.A. Kreidberg, and R.O. Hynes. 2000. Mouse keratinocytes immortalized with large T antigen acquire alpha3beta1 integrin-dependent secretion of MMP-9/gelatinase B. J Cell Sci. 113 ( Pt 16):2909-21.
Egeblad, M., and Z. Werb. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161-74.
Fidler, I.J. 1970. Metastasis: guantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst. 45:773-82.
Fidler, I.J. 1975. Biological behavior of malignant melanoma cells correlated to their survival in vivo. Cancer Res. 35:218-24.
Fidler, I.J. 1990. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 50:6130-8.
Finkel, T. 2001. Reactive oxygen species and signal transduction. IUBMB Life. 52:3-6.
Frost, J.A., T.D. Geppert, M.H. Cobb, and J.R. Feramisco. 1994. A requirement for extracellular signal-regulated kinase (ERK) function in the activation of AP-1 by Ha-Ras, phorbol 12-myristate 13-acetate, and serum. Proc Natl Acad Sci U S A. 91:3844-8.
Guo, W., and F.G. Giancotti. 2004. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 5:816-26.
Gupta, A., S.F. Rosenberger, and G.T. Bowden. 1999. Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines. Carcinogenesis. 20:2063-73.
Halliwell, B. 1996. Free radicals, proteins and DNA: oxidative damage versus redox regulation. Biochem Soc Trans. 24:1023-7.
Hanahan, D., and J. Folkman. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353-64.
Ho, J., S. Zheng, S.A. Comhair, C. Farver, and S.C. Erzurum. 2001. Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res. 61:8578-85.
Ho, Y.S., M. Gargano, J. Cao, R.T. Bronson, I. Heimler, and R.J. Hutz. 1998. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem. 273:7765-9.
Hu, Y., D.G. Rosen, Y. Zhou, L. Feng, G. Yang, J. Liu, and P. Huang. 2005. Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress. J Biol Chem. 280:39485-92.
Huang, T.T., M. Yasunami, E.J. Carlson, A.M. Gillespie, A.G. Reaume, E.K. Hoffman, P.H. Chan, R.W. Scott, and C.J. Epstein. 1997. Superoxide-mediated cytotoxicity in superoxide dismutase-deficient fetal fibroblasts. Arch Biochem Biophys. 344:424-32.
Hynes, R.O. 2003. Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants-or both? Cell. 113:821-3.
Inoue, T., M. Yashiro, S. Nishimura, K. Maeda, T. Sawada, Y. Ogawa, M. Sowa, and K.H. Chung. 1999. Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer. Int J Mol Med. 4:73-7.
Janssen, Y.M., J.P. Marsh, M.P. Absher, D. Hemenway, P.M. Vacek, K.O. Leslie, P.J. Borm, and B.T. Mossman. 1992. Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica. J Biol Chem. 267:10625-30.
Janssen, Y.M., B. Van Houten, P.J. Borm, and B.T. Mossman. 1993. Cell and tissue responses to oxidative damage. Lab Invest. 69:261-74.
Jia, Y., Z.Z. Zeng, S.M. Markwart, K.F. Rockwood, K.M. Ignatoski, S.P. Ethier, and D.L. Livant. 2004. Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Res. 64:8674-81.
Kang, Y., P.M. Siegel, W. Shu, M. Drobnjak, S.M. Kakonen, C. Cordon-Cardo, T.A. Guise, and J. Massague. 2003. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 3:537-49.
Kinnula, V.L., and J.D. Crapo. 2004. Superoxide dismutases in malignant cells and human tumors. Free Radic Biol Med. 36:718-44.
Lakari, E., P. Paakko, and V.L. Kinnula. 1998. Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Am J Respir Crit Care Med. 158:589-96.
Lam, E.W., R. Zwacka, E.A. Seftor, D.R. Nieva, B.L. Davidson, J.F. Engelhardt, M.J. Hendrix, and L.W. Oberley. 1999. Effects of antioxidant enzyme overexpression on the invasive phenotype of hamster cheek pouch carcinoma cells. Free Radic Biol Med. 27:572-9.
Lebovitz, R.M., H. Zhang, H. Vogel, J. Cartwright, Jr., L. Dionne, N. Lu, S. Huang, and M.M. Matzuk. 1996. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A. 93:9782-7.
Lee, S.R., K.S. Kwon, S.R. Kim, and S.G. Rhee. 1998. Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem. 273:15366-72.
Liotta, L.A., P.S. Steeg, and W.G. Stetler-Stevenson. 1991. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 64:327-36.
Malafa, M., J. Margenthaler, B. Webb, L. Neitzel, and M. Christophersen. 2000. MnSOD expression is increased in metastatic gastric cancer. J Surg Res. 88:130-4.
Martindale, J.L., and N.J. Holbrook. 2002. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 192:1-15.
Mates, J.M., C. Perez-Gomez, and I. Nunez de Castro. 1999. Antioxidant enzymes and human diseases. Clin Biochem. 32:595-603.
McDonald, D.M., and P. Baluk. 2002. Significance of blood vessel leakiness in cancer. Cancer Res. 62:5381-5.
Meng, T.C., T. Fukada, and N.K. Tonks. 2002. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell. 9:387-99.
Mizutani, K., K. Kofuji, and K. Shirouzu. 2000. The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of gastric cancer. Surg Today. 30:614-21.
Mori, K., M. Shibanuma, and K. Nose. 2004. Invasive potential induced under long-term oxidative stress in mammary epithelial cells. Cancer Res. 64:7464-72.
Nelson, K.K., A.C. Ranganathan, J. Mansouri, A.M. Rodriguez, K.M. Providence, J.L. Rutter, K. Pumiglia, J.A. Bennett, and J.A. Melendez. 2003. Elevated sod2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis. Clin Cancer Res. 9:424-32.
Nobes, C.D., and A. Hall. 1999. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol. 144:1235-44.
Osada, H., and T. Takahashi. 2002. Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene. 21:7421-34.
Palazzotti, B., G. Pani, R. Colavitti, M.E. De Leo, B. Bedogni, S. Borrello, and T. Galeotti. 1999. Increased growth capacity of cervical-carcinoma cells over-expressing manganous superoxide dismutase. Int J Cancer. 82:145-50.
Poli, G., G. Leonarduzzi, F. Biasi, and E. Chiarpotto. 2004. Oxidative stress and cell signalling. Curr Med Chem. 11:1163-82.
Postma, M., L. Bosgraaf, H.M. Loovers, and P.J. Van Haastert. 2004. Chemotaxis: signalling modules join hands at front and tail. EMBO Rep. 5:35-40.
Qian, Y., K.J. Liu, Y. Chen, D.C. Flynn, V. Castranova, and X. Shi. 2005. Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration through actin filament reorganization. J Biol Chem. 280:3875-84.
Qian, Y., J. Luo, S.S. Leonard, G.K. Harris, L. Millecchia, D.C. Flynn, and X. Shi. 2003. Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesis. J Biol Chem. 278:16189-97.
Rajagopalan, S., X.P. Meng, S. Ramasamy, D.G. Harrison, and Z.S. Galis. 1996. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 98:2572-9.
Ramaswamy, S., K.N. Ross, E.S. Lander, and T.R. Golub. 2003. A molecular signature of metastasis in primary solid tumors. Nat Genet. 33:49-54.
Ranganathan, A.C., K.K. Nelson, A.M. Rodriguez, K.H. Kim, G.B. Tower, J.L. Rutter, C.E. Brinckerhoff, T.T. Huang, C.J. Epstein, J.J. Jeffrey, and J.A. Melendez. 2001. Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation. J Biol Chem. 276:14264-70.
Safford, S.E., T.D. Oberley, M. Urano, and D.K. St Clair. 1994. Suppression of fibrosarcoma metastasis by elevated expression of manganese superoxide dismutase. Cancer Res. 54:4261-5.
Shimoda-Matsubayashi, S., H. Matsumine, T. Kobayashi, Y. Nakagawa-Hattori, Y. Shimizu, and Y. Mizuno. 1996. Structural Dimorphism in the Mitochondrial Targeting Sequence in the Human Manganese Superoxide Dismutase Gene. Biochem Biophys Res Commun. 226:561-5.
Siwik, D.A., P.J. Pagano, and W.S. Colucci. 2001. Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts. Am J Physiol Cell Physiol. 280:C53-60.
Spallarossa, P., P. Altieri, S. Garibaldi, G. Ghigliotti, C. Barisione, V. Manca, P. Fabbi, A. Ballestrero, C. Brunelli, and A. Barsotti. 2006. Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: The role of MAP kinases and NAD(P)H oxidase. Cardiovasc Res. 69:736-45.
Szatrowski, T.P., and C.F. Nathan. 1991. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51:794-8.
Toh, Y., S. Kuninaka, T. Oshiro, Y. Ikeda, H. Nakashima, H. Baba, S. Kohnoe, T. Okamura, M. Mori, and K. Sugimachi. 2000. Overexpression of manganese superoxide dismutase mRNA may correlate with aggressiveness in gastric and colorectal adenocarcinomas. Int J Oncol. 17:107-12.
Torres, M. 2003. Mitogen-activated protein kinase pathways in redox signaling. Front Biosci. 8:d369-91.
Warner, B.B., L. Stuart, S. Gebb, and J.R. Wispe. 1996. Redox regulation of manganese superoxide dismutase. Am J Physiol. 271:L150-8.
Weber, D.S., Y. Taniyama, P. Rocic, P.N. Seshiah, M.A. Dechert, W.T. Gerthoffer, and K.K. Griendling. 2004. Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration. Circ Res. 94:1219-26.
Weisiger, R.A., and I. Fridovich. 1973. Superoxide dismutase. Organelle specificity. J Biol Chem. 248:3582-92.
Wenk, J., P. Brenneisen, M. Wlaschek, A. Poswig, K. Briviba, T.D. Oberley, and K. Scharffetter-Kochanek. 1999. Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the AP-1-mediated induction of matrix-degrading metalloprotease-1. J Biol Chem. 274:25869-76.
Westermarck, J., and V.M. Kahari. 1999. Regulation of matrix metalloproteinase expression in tumor invasion. Faseb J. 13:781-92.
Westermarck, J., S.P. Li, T. Kallunki, J. Han, and V.M. Kahari. 2001. p38 mitogen-activated protein kinase-dependent activation of protein phosphatases 1 and 2A inhibits MEK1 and MEK2 activity and collagenase 1 (MMP-1) gene expression. Mol Cell Biol. 21:2373-83.
Williams, M.D., H. Van Remmen, C.C. Conrad, T.T. Huang, C.J. Epstein, and A. Richardson. 1998. Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem. 273:28510-5.
Woodhouse, E.C., R.F. Chuaqui, and L.A. Liotta. 1997. General mechanisms of metastasis. Cancer. 80:1529-37.
Xu, D., Rovira, II, and T. Finkel. 2002. Oxidants painting the cysteine chapel: redox regulation of PTPs. Dev Cell. 2:251-2.
Yeh, C.C., X.S. Wan, and D.K. St Clair. 1998. Transcriptional regulation of the 5' proximal promoter of the human manganese superoxide dismutase gene. DNA Cell Biol. 17:921-30.
Yoon, S.O., S.J. Park, S.Y. Yoon, C.H. Yun, and A.S. Chung. 2002. Sustained production of H(2)O(2) activates pro-matrix metalloproteinase-2 through receptor tyrosine kinases/phosphatidylinositol 3-kinase/NF-kappa B pathway. J Biol Chem. 277:30271-82.
Yoshida, M., T.R. Korfhagen, and J.A. Whitsett. 2001. Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol. 166:7514-9.
Zhang, H.J., T. Yan, T.D. Oberley, and L.W. Oberley. 1999. Comparison of effects of two polymorphic variants of manganese superoxide dismutase on human breast MCF-7 cancer cell phenotype. Cancer Res. 59:6276-83.
Zhang, H.J., W. Zhao, S. Venkataraman, M.E. Robbins, G.R. Buettner, K.C. Kregel, and L.W. Oberley. 2002. Activation of matrix metalloproteinase-2 by overexpression of manganese superoxide dismutase in human breast cancer MCF-7 cells involves reactive oxygen species. J Biol Chem. 277:20919-26.
Zhang, N. 1996. Characterization of the 5' flanking region of the human MnSOD gene. Biochem Biophys Res Commun. 220:171-80.
Zyad, A., J. Benard, T. Tursz, R. Clarke, and S. Chouaib. 1994. Resistance to TNF-alpha and adriamycin in the human breast cancer MCF-7 cell line: relationship to MDR1, MnSOD, and TNF gene expression. Cancer Res. 54:825-31.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32669-
dc.description.abstract癌細胞的轉移(metastasis)一直是造成癌症病患致死的主要原因,因此了解癌細胞的轉移機制一直是個重要的研究課題。在過去的文獻中指出,過氧化氫 (H2O2)和癌細胞的惡化有密切的關係,在較惡化的癌細胞體內,H2O2 產生的量的確有明顯上升的情形。在癌細胞惡化的過程中,H2O2可以藉由活化不同的訊息傳遞途徑去活化 matrix metalloproteinase (MMP) 的釋放以及增加癌細胞貼附到細胞外間質 (Extracellular matrix) 的能力, 進而造成癌細胞移動能力以及入侵能力的上升。 在本實驗室稍早的研究中,我們成功的使用Boyden chamber assay從 A431 P 細胞中挑選出一群具有高度入侵性的癌細胞,我們將它們命名為 A431 III。比較這兩株癌細胞之後,我們發現 A431 III 相較於 A431 P 產生較多的 H2O2 ,這個原因可能是由於 A431 III 細胞內抗氧化酵素的表現量改變的關係造成的,包括了MnSOD 的上升以及 Catalase 的下降。由於這些抗氧化素表現量的變化是平衡細胞內 H2O2 的一個重要防禦機制。因此在本實驗中,我們進一步的使用了 MnSOD siRNA 來抑制 MnSOD 表現量,間接的促使細胞內 H2O2 產生的量上升。這些累積在細胞中的 H2O2 促進了癌細胞惡化情形的上升,包括移動能力入侵能力,貼附能力,以及 MMP 釋放的增加。這些結果顯示了 A431 III 入侵能力的上升可能是經由 H2O2 表現量的上升,進而活化細胞移動能力與 增加 MMP 的分泌所造成的結果。zh_TW
dc.description.abstractTumor metastasis has always been the main factor that causes the death of cancer patients, thus it is important to realize the mechanism of cancer metastasis. It has been appreciated for a number of years that H2O2 production is increased in malignant cancer cells. During tumor progression, H2O2 can activate MMP activity, cell-ECM adhesion, and subsequently promotes the capability of cell migration and cell invasion. The signaling pathway involved in these processes are thought to be achieved through redox modification of signaling molecules such as protein kinases and transcription factors. In the previous study from our laboratory, we have selected highly invasive tumor cell sub-line A431III from A431 by using Boyden Chamber Assay (unpublished data). In this study, we take the advantage of this highly invasive sub-line to further explore the role of H2O2 in cancer cells. We find that H2O2 production is increased in A431III sub-line compared to A431P. This result may attribute to differential expression of antioxidants, which were important in balancing cellular H2O2 levels. We find that MnSOD expression is increased whereas catalase is decreased in A431III sub-line compared to A431P. To further investigate the role of H2O2, we used MnSOD siRNA to suppress the expression of MnSOD. Interestingly, the amounts of H2O2 production were increased after transfection of MnSOD siRNA. The elevated H2O2 lead to increase the capabilities of cell migration, cell invasion, cell-ECM adhesion, and MMP expression. These results described above suggesting that H2O2 may act as an important messenger in regulating cell metastasis in A431 III sub-line.en
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dc.description.tableofcontents中文摘要 I
ABSTRACT II
=================================================================
INTRODUCTION 1
Mechanisms of Cancer Metastasis 1
Mechanisms of cancer invasion 2
Models of metastatic potential within primary tumors and In vitro invasion assay 2
ROS and Cancer 4
Matrix Metalloproteinase (MMP) 5
Major antioxidant pathways in mammalian cells 6
Superoxide Dismutase (SOD) 7
Redox Regulation of MAPK and MMP by MnSOD 9
=================================================================
MATERIALS AND METHODS 18
Materials and Antibodies 18
Cell Culture 18
Crystal Violet Staining 18
Wound Healing Assay 19
Migration Assay 19
Invasion Assay 19
Adhesion Assay 20
SiRNA transfection 21
Growth experiment 21
Cell Lysate Preparation 22
Western Blot Analysis 22
SOD Activity Gel Assay 22
Zymography 23
ROS Measurement 23
RT-PCR mRNA Analysis 24
RESULTS 26
Highly invasive A431III sub-line exhibit higher H2O2 production 26
Antioxidant activity and protein expression 26
Identification of increased MMP secretion in highly invasive tumor cell line 27
Supression of MnSOD expression and accumulation of H2O2 by siRNA 28
Comparison of cell proliferation in A431P and A431III sub-line with different MnSOD expression levels 30
Accumulation of ROS by MnSOD siRNA promote cell metastasis and migration 30
Accumulated ROS by MnSOD siRNA mediate cell adhesion 32
Accumulation of ROS by suppression of MnSOD expression increased cell invasion and induced MMP expression 33
DPI delayed cell migration and cell adhesion through the inhibition of ROS production 34
=================================================================
DISCUSSION 43
=================================================================
REFERENCES 47





Figure Contents
Figure I. The process of tumor metastasis……………………………………………12
Figure II. Models of metastatic potential within primary tumors and in vitro invasion assay………………………………………………………………………………….13
Figure III. ROS regulated multiple mechanisms related to cancer progression.............14
Figure IV. MMP family……………………………………………………………......15
Figure V. Multiple antioxidants participate in the scavenging ROS.............................16
Figure VI. Redox Regulation of MAPK and MMP by MnSOD....................................17
Figure 1. Highly invasive A431 III sub-line exhibited higher H2O2 production may through regulation of antioxidants expression………………………………………...36
Figure 2. Highly invasive A431 III sub-line secreted more MMP than A431 P………37
Figure 3. Suppression of MnSOD expression and accumulation of H2O2 by MnSOD siRNA………………………………………………………………………….38
Figure 4. Accumulation of ROS by MnSOD siRNA increases cell migration……...39
Figure 5. Accumulated ROS by MnSOD siRNA mediate cell adhesion……………40
Figure 6. Accumulation of ROS by suppression of MnSOD expression increased cell invasion and induced MMP expression………………………………………………41
Figure 7. DPI delayed cell migration and cell adhesion through the inhibition of ROS production……………………………………………………….................................42
dc.language.isozh-TW
dc.subject過氧化氫zh_TW
dc.subjectMnSODzh_TW
dc.subjectMnSODen
dc.subjectH2O2en
dc.title高度入侵性A431癌細胞中過氧化氫之生成及MnSOD表現量對細胞轉移及入侵能力探討zh_TW
dc.titleH2O2 production and MnSOD expression in highly invasive potential A431 sub-line:Role in cell migration and invasionen
dc.typeThesis
dc.date.schoolyear94-2
dc.description.degree碩士
dc.contributor.oralexamcommittee黃銓珍,黃娟娟,黃彬彬,周志銘
dc.subject.keyword過氧化氫,MnSOD,zh_TW
dc.subject.keywordH2O2,MnSOD,en
dc.relation.page54
dc.rights.note有償授權
dc.date.accepted2006-07-26
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科學研究所zh_TW
顯示於系所單位:生化科學研究所

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