請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33435完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭明良 | |
| dc.contributor.author | Hou-Jung Shih | en |
| dc.contributor.author | 施后容 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:40:22Z | - |
| dc.date.available | 2006-08-03 | |
| dc.date.copyright | 2006-08-03 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-19 | |
| dc.identifier.citation | References
Arnesen, T., Anderson, D., Baldersheim, C., Lanotte, M., Varhaug, J. E., and Lillehaug, J. R. (2005). Identification and characterization of the human ARD1-NATH protein acetyltransferase complex. Biochem J 386, 433-443. Arnesen, T., Gromyko, D., Pendino, F., Ryningen, A., Varhaug, J. E., and Lillehaug, J. R. (2006). Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex. Oncogene. Asaumi, M., Iijima, K., Sumioka, A., Iijima-Ando, K., Kirino, Y., Nakaya, T., and Suzuki, T. (2005). Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion. J Biochem (Tokyo) 137, 147-155. Bannister, A. J., and Miska, E. A. (2000). Regulation of gene expression by transcription factor acetylation. Cell Mol Life Sci 57, 1184-1192. Bar-Sagi, D., and Hall, A. (2000). Ras and Rho GTPases: a family reunion. Cell 103, 227-238. Barlev, N. A., Liu, L., Chehab, N. H., Mansfield, K., Harris, K. G., Halazonetis, T. D., and Berger, S. L. (2001). Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 8, 1243-1254. Barnes, P. J., Adcock, I. M., and Ito, K. (2005). Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J 25, 552-563. Bilton, R., Mazure, N., Trottier, E., Hattab, M., Dery, M. A., Richard, D. E., Pouyssegur, J., and Brahimi-Horn, M. C. (2005). Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF. J Biol Chem 280, 31132-31140. Boyes, J., Byfield, P., Nakatani, Y., and Ogryzko, V. (1998). Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 396, 594-598. Braun, H., Koop, R., Ertmer, A., Nacht, S., and Suske, G. (2001). Transcription factor Sp3 is regulated by acetylation. Nucleic Acids Res 29, 4994-5000. Brown, J. L., and Roberts, W. K. (1976). Evidence that approximately eighty per cent of the soluble proteins from Ehrlich ascites cells are Nalpha-acetylated. J Biol Chem 251, 1009-1014. Brown, M. C., and Turner, C. E. (2004). Paxillin: adapting to change. Physiol Rev 84, 1315-1339. Carragher, N. O., and Frame, M. C. (2004). Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion. Trends Cell Biol 14, 241-249. Chambers, A. F., Groom, A. C., and MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2, 563-572. Chang, C. C., Shih, J. Y., Jeng, Y. M., Su, J. L., Lin, B. Z., Chen, S. T., Chau, Y. P., Yang, P. C., and Kuo, M. L. (2004). Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis. J Natl Cancer Inst 96, 364-375. Chu, Y. W., Yang, P. C., Yang, S. C., Shyu, Y. C., Hendrix, M. J., Wu, R., and Wu, C. W. (1997). Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 17, 353-360. Cohen, H. Y., Lavu, S., Bitterman, K. J., Hekking, B., Imahiyerobo, T. A., Miller, C., Frye, R., Ploegh, H., Kessler, B. M., and Sinclair, D. A. (2004). Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol Cell 13, 627-638. Di Gennaro, E., Bruzzese, F., Caraglia, M., Abruzzese, A., and Budillon, A. (2004). Acetylation of proteins as novel target for antitumor therapy: review article. Amino Acids 26, 435-441. Driessen, H. P., de Jong, W. W., Tesser, G. I., and Bloemendal, H. (1985). The mechanism of N-terminal acetylation of proteins. CRC Crit Rev Biochem 18, 281-325. Fidler, I. J. (2002). Critical determinants of metastasis. Semin Cancer Biol 12, 89-96. Fisher, T. S., Etages, S. D., Hayes, L., Crimin, K., and Li, B. (2005). Analysis of ARD1 function in hypoxia response using retroviral RNA interference. J Biol Chem 280, 17749-17757. Friedl, P., and Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3, 362-374. Fu, M., Wang, C., Wang, J., Zafonte, B. T., Lisanti, M. P., and Pestell, R. G. (2002). Acetylation in hormone signaling and the cell cycle. Cytokine Growth Factor Rev 13, 259-276. Gautschi, M., Just, S., Mun, A., Ross, S., Rucknagel, P., Dubaquie, Y., Ehrenhofer-Murray, A., and Rospert, S. (2003). The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides. Mol Cell Biol 23, 7403-7414. Geiger, B., and Bershadsky, A. (2001). Assembly and mechanosensory function of focal contacts. Curr Opin Cell Biol 13, 584-592. Geissenhoner, A., Weise, C., and Ehrenhofer-Murray, A. E. (2004). Dependence of ORC silencing function on NatA-mediated Nalpha acetylation in Saccharomyces cerevisiae. Mol Cell Biol 24, 10300-10312. Greenlee, R. T., Hill-Harmon, M. B., Murray, T., and Thun, M. (2001). Cancer statistics, 2001. CA Cancer J Clin 51, 15-36. Gu, W., and Roeder, R. G. (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90, 595-606. Gustavsson, A., Yuan, M., and Fallman, M. (2004). Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation. J Biol Chem 279, 22893-22901. Hall, A., and Nobes, C. D. (2000). Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos Trans R Soc Lond B Biol Sci 355, 965-970. Hoffmann, D., Rivenson, A., and Hecht, S. S. (1996). The biological significance of tobacco-specific N-nitrosamines: smoking and adenocarcinoma of the lung. Crit Rev Toxicol 26, 199-211. Hung, H. L., Lau, J., Kim, A. Y., Weiss, M. J., and Blobel, G. A. (1999). CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Mol Cell Biol 19, 3496-3505. Jeong, J. W., Bae, M. K., Ahn, M. Y., Kim, S. H., Sohn, T. K., Bae, M. H., Yoo, M. A., Song, E. J., Lee, K. J., and Kim, K. W. (2002). Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 111, 709-720. Keely, P. J., Rusyn, E. V., Cox, A. D., and Parise, L. V. (1999). R-Ras signals through specific integrin alpha cytoplasmic domains to promote migration and invasion of breast epithelial cells. J Cell Biol 145, 1077-1088. Kouzarides, T. (1999). Histone acetylases and deacetylases in cell proliferation. Curr Opin Genet Dev 9, 40-48. Kouzarides, T. (2000). Acetylation: a regulatory modification to rival phosphorylation? Embo J 19, 1176-1179. Lauffenburger, D. A., and Horwitz, A. F. (1996). Cell migration: a physically integrated molecular process. Cell 84, 359-369. Lee, F. J., Lin, L. W., and Smith, J. A. (1989). N alpha acetylation is required for normal growth and mating of Saccharomyces cerevisiae. J Bacteriol 171, 5795-5802. Mahlknecht, U., and Hoelzer, D. (2000). Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med 6, 623-644. Martinez-Balbas, M. A., Bauer, U. M., Nielsen, S. J., Brehm, A., and Kouzarides, T. (2000). Regulation of E2F1 activity by acetylation. Embo J 19, 662-671. McLean, G. W., Carragher, N. O., Avizienyte, E., Evans, J., Brunton, V. G., and Frame, M. C. (2005). The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer 5, 505-515. Mitchison, T. J., and Cramer, L. P. (1996). Actin-based cell motility and cell locomotion. Cell 84, 371-379. Mitra, S. K., Hanson, D. A., and Schlaepfer, D. D. (2005). Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6, 56-68. Mullen, J. R., Kayne, P. S., Moerschell, R. P., Tsunasawa, S., Gribskov, M., Colavito-Shepanski, M., Grunstein, M., Sherman, F., and Sternglanz, R. (1989). Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast. Embo J 8, 2067-2075. Neuwald, A. F., and Landsman, D. (1997). GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein. Trends Biochem Sci 22, 154-155. Nobes, C. D., and Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53-62. Ogryzko, V. V., Kotani, T., Zhang, X., Schiltz, R. L., Howard, T., Yang, X. J., Howard, B. H., Qin, J., and Nakatani, Y. (1998). Histone-like TAFs within the PCAF histone acetylase complex. Cell 94, 35-44. Park, E. C., and Szostak, J. W. (1992). ARD1 and NAT1 proteins form a complex that has N-terminal acetyltransferase activity. Embo J 11, 2087-2093. Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985). Structures of N-terminally acetylated proteins. Eur J Biochem 152, 523-527. Polevoda, B., and Sherman, F. (2003). N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins. J Mol Biol 325, 595-622. Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T., and Horwitz, A. R. (2003). Cell migration: integrating signals from front to back. Science 302, 1704-1709. Sartorelli, V., Puri, P. L., Hamamori, Y., Ogryzko, V., Chung, G., Nakatani, Y., Wang, J. Y., and Kedes, L. (1999). Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol Cell 4, 725-734. Sastry, S. K., and Burridge, K. (2000). Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res 261, 25-36. Shih, J. Y., Lee, Y. C., Yang, S. C., Hong, T. M., Huang, C. Y., and Yang, P. C. (2003). Collapsin response mediator protein-1: a novel invasion-suppressor gene. Clin Exp Metastasis 20, 69-76. Sonnichsen, B., Koski, L. B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A. M., Artelt, J., Bettencourt, P., Cassin, E., et al. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462-469. Spike, B. T., Dirlam, A., Dibling, B. C., Marvin, J., Williams, B. O., Jacks, T., and Macleod, K. F. (2004). The Rb tumor suppressor is required for stress erythropoiesis. Embo J 23, 4319-4329. Steeg, P. S., Bevilacqua, G., Sobel, M. E., and Liotta, L. A. (1991). Identification and characterization of differentially expressed genes in tumor metastasis: the nm23 gene. Basic Life Sci 57, 355-360; discussion 360-351. Su, J. L., Yang, C. Y., Shih, J. Y., Wei, L. H., Hsieh, C. Y., Jeng, Y. M., Wang, M. Y., Yang, P. C., and Kuo, M. L. (2006). Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma. Cancer Res 66, 2553-2561. Sugiura, N., Adams, S. M., and Corriveau, R. A. (2003). An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development. J Biol Chem 278, 40113-40120. Takai, Y., Sasaki, T., and Matozaki, T. (2001). Small GTP-binding proteins. Physiol Rev 81, 153-208. Tribioli, C., Mancini, M., Plassart, E., Bione, S., Rivella, S., Sala, C., Torri, G., and Toniolo, D. (1994). Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae. Hum Mol Genet 3, 1061-1067. Waltzer, L., and Bienz, M. (1998). Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature 395, 521-525. Wang, X., Connelly, J. J., Wang, C. L., and Sternglanz, R. (2004). Importance of the Sir3 N terminus and its acetylation for yeast transcriptional silencing. Genetics 168, 547-551. Whiteway, M., Freedman, R., Van Arsdell, S., Szostak, J. W., and Thorner, J. (1987). The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus. Mol Cell Biol 7, 3713-3722. Whiteway, M., and Szostak, J. W. (1985). The ARD1 gene of yeast functions in the switch between the mitotic cell cycle and alternative developmental pathways. Cell 43, 483-492. Woodhouse, E. C., Chuaqui, R. F., and Liotta, L. A. (1997). General mechanisms of metastasis. Cancer 80, 1529-1537. Zhang, W., and Bieker, J. J. (1998). Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci U S A 95, 9855-9860. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33435 | - |
| dc.description.abstract | 肺癌為世界十大癌症死因之首，導致肺癌死亡率居高的原因，主要為癌細胞之遠端轉移率高而造成治療失敗。因此研究抑制癌細胞轉移之機轉，在癌症治療領域佔有重要的角色。癌細胞轉移的病理機制包括細胞移動、浸襲、血管新生、及細胞增生。不同型態的細胞轉移會受到不同的機轉調控。找出抑制腫瘤浸襲基因並釐清其機制，可做為作為病理診斷上的新方法，及未來治療癌症的方向。
F-肌動蛋白結構的改變是導致細胞移動的主要機轉。F-肌動蛋白的重組主要受到小型G蛋白質所調控，如Rho、Rac1及Cdc42。小型G蛋白活性可傳遞細胞外的化學訊息至下游的接受者，而使細胞骨架結構重組，因此抑制小型G蛋白質酵素活性可減少癌細胞轉移及浸襲的能力。 ARD1 在1985年即被發現在酵母菌中扮演著轉換細胞有絲分裂及發育機轉之角色，ARD1和其共同作用者NATH可形成一個穩定的結構，此結構具有N基乙醯轉移酵素之活性，並參與許多生物性功能如細胞分化，熱敏感性，細胞凋亡等。本篇研究結果顯示，臨床上分析ARD1蛋白表現量較低的病人，與癌病惡性度較高，有淋巴轉移，較早癌病復發率及較短存活時間有正相關。ARD1在非肺癌腫瘤部位的蛋白表現量較腫瘤組織表現量高，在統計上也有顯著的意義（p<0.05）。在體外細胞株實驗當中，ARD1的核糖核酸及蛋白表現量和轉移浸襲能力有高度負相關性。在ARD1過度表現之轉殖細胞株中發現顯著降低細胞的轉移及浸襲能力；相反的在ARD1剔除轉殖株中則促進癌細胞轉移能力。進一步探討ARD1所調控之轉移能力之機轉則發現，ARD1可降低小型G蛋白質的活性，而導致F-肌動蛋白骨架重整，降低filopodia的形成即使細胞轉變為非轉移性型態而有效抑制細胞轉移能力。我們也證明了ARD1本身之N基乙醯轉移酵素活性並不影響其調控細胞轉移及浸襲之能力。最後藉由動物實驗，再次印證ARD1在活體實驗當中也有效抑制癌細胞轉移能力。因此，ARD1為一個新發現之抑癌基因並可作為將來治療癌症轉移的標的因子。 | zh_TW |
| dc.description.abstract | Lung cancer is by far the most common cause of cancer death in the world, and metastasis is the major cause of treatment failure and death in cancer patients. The pathogenesis of cancer metastasis involves cell migration, invasion, angiogenesis, and cell proliferation. Different types of cell migration are regulated by different mechanisms. Identification of novel tumor migration-associated genes and elucidation of their mechanism of action may provide new insights into the pathogenesis and management of cancer metastasis.
Reorganization of the actin cytoskeleton is the primary mechanism of cell motility and is essential for most types of cell migration. Actin reorganization is regulated by Rho family small GTPases such as Rho, Rac, and Cdc42. These small GTPases transmit extracellular chemotactic signals to downstream effectors. Inhibition of Rho family small GTPase signaling suppresses the migration and invasion of cancer cells. Thus, control of cell migration via the actin cytoskeleton provides the possibility of regulating cancer cell migration and metastasis. Arrest defective protein 1 (ARD1) is first described in Saccharomyces cerevisiae. It is characterized as an N-acetyltransferase and forms heterodimer with human N-acetyltransferase (NATH). The ARD1-NATH complex shows N-acetyltransferase activity and involves in many biological processes such as cell cycle regulation, viability, temperature sensitivity, and differentiation. We recently identified ARD1 as a novel migration suppressor and a prognosis marker of metastasist in lung adenocarcinoma patients. In the present study, we found that ARD1 was expressed higher in non-tumor part than matched tumor part of lung adenocarcinoma patients and reversely correlated with the migration and invasion abilities in lung adenocarcinoma cell lines. We demonstrated that ARD1 inhibited migratory and invasive abilities, and depolymerized F-actin structure through reducing Rho family Cdc42 and Rac1 GTPases activities. Moreover, in vivo animal model showed that ARD1 inhibited distal organ metastasis and primary tumorigenesis. In conclusion, we considered ARD1 as a tumor suppressor gene and it inhibited cancer cell migration and metastasis through reducing Cdc42 and Rac1 activity together with F-actin structure reorganization. Therefore, ARD1 may be a potential target for cancer treatment. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:40:22Z (GMT). No. of bitstreams: 1 ntu-95-R93447004-1.pdf: 3832625 bytes, checksum: f9f768e81fe065714bfd35af60aadb29 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | Content
中文摘要………………………………………………………………………………2 Abstract………………………………………………………………………………..3 Preface………………………………………………………………………………...5 Ⅰ. Human Lung adenocarcinoma…………………………………………5 Ⅱ. Tumor metastasis……………………………………………………..…7 Ⅲ. Arrest defective protein 1 (ARD1)………………………………….….9 Ⅳ. Rho family small G proteins……………………………………….…..11 Chapter：ARD1 Inhibits Lung Adenocarcinoma Metastasis through reducing Cdc42/Rac1 Activity and Reorganizing F-actin Cytoskeleton Structure. Introduction………………………………………………………………..13 Materials and Methods……………………………………………………17 Results……………………………………………………………………...26 Discussion……………………………………………………………….…38 Figures and Figure Legends……………………………………………...42 Tables………………………………………………………………….…...67 Reference………………………………………………………………..…68 | |
| dc.language.iso | en | |
| dc.subject | 細胞骨架 | zh_TW |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | metastasis | en |
| dc.subject | GTPase | en |
| dc.subject | cytoskeleton | en |
| dc.subject | ARD1 | en |
| dc.title | ARD1抑制人類肺腺癌轉移角色之探討 | zh_TW |
| dc.title | ARD1 Inhibits Lung Adenocarcinama Metastasis through Reducing Cdc42/Rac1 Activity and Reorganizing F-actin Cytoskeleton Structure. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 翁一鳴,王朝鍾,鄭安理,莊雙恩,林明燦 | |
| dc.subject.keyword | 肺癌,轉移,細胞骨架, | zh_TW |
| dc.subject.keyword | ARD1,metastasis,cytoskeleton,GTPase, | en |
| dc.relation.page | 72 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-95-1.pdf 未授權公開取用 | 3.74 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。