請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23648
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡錦華 | |
dc.contributor.author | Ya-Ching Chou | en |
dc.contributor.author | 周雅菁 | zh_TW |
dc.date.accessioned | 2021-06-08T05:06:44Z | - |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-06-29 | |
dc.identifier.citation | Ai, M. D., Li, L. L., Zhao, X. R., Wu, Y., Gong, J. P. & Cao, Y. (2005). Regulation of survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines. Cell Res 15, 777-784.
Allday, M. J. & Crawford, D. H. (1988). Role of epithelium in EBV persistence and pathogenesis of B-cell tumours. Lancet 1, 855-857. Baer, R., Bankier, A. T., Biggin, M. D., Deininger, P. L., Farrell, P. J., Gibson, T. J., Hatfull, G., Hudson, G. S., Satchwell, S. C., Seguin, C. & et al. (1984). DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310, 207-211. Banu, N., Price, D. J., London, R., Deng, B., Mark, M., Godowski, P. J. & Avraham, H. (1996). Modulation of megakaryocytopoiesis by human macrophage-stimulating protein, the ligand for the RON receptor. J Immunol 156, 2933-2940. Bardella, C., Costa, B., Maggiora, P., Patane, S., Olivero, M., Ranzani, G. N., De Bortoli, M., Comoglio, P. M. & Di Renzo, M. F. (2004). Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression. Cancer Res 64, 5154-5161. Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J. & Garcia De Herreros, A. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2, 84-89. Bezerra, J. A., Laney, D. W., Jr. & Degen, S. J. (1994). Increased expression of mRNA for hepatocyte growth factor-like protein during liver regeneration and inflammation. Biochem Biophys Res Commun 203, 666-673. Bieging, K. T., Swanson-Mungerson, M., Amick, A. C. & Longnecker, R. (2010). Epstein-Barr virus in Burkitt's lymphoma: a role for latent membrane protein 2A. Cell Cycle 9, 901-908. Blume-Jensen, P. & Hunter, T. (2001). Oncogenic kinase signalling. Nature 411, 355-365. Bolos, V., Peinado, H., Perez-Moreno, M. A., Fraga, M. F., Esteller, M. & Cano, A. (2003). The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 116, 499-511. Bouillie, S., Barel, M. & Frade, R. (1999). Signaling through the EBV/C3d receptor (CR2, CD21) in human B lymphocytes: activation of phosphatidylinositol 3-kinase via a CD19-independent pathway. J Immunol 162, 136-143. Brennan, P., Mehl, A. M., Jones, M. & Rowe, M. (2002). Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells. Oncogene 21, 1263-1271. Burkitt, D. (1962). A children's cancer dependent on climatic factors. Nature 194, 232-234. Burnett, S., Jareborg, N. & DiMaio, D. (1992). Localization of bovine papillomavirus type 1 E5 protein to transformed basal keratinocytes and permissive differentiated cells in fibropapilloma tissue. Proc Natl Acad Sci U S A 89, 5665-5669. Camp, E. R., Yang, A., Gray, M. J., Fan, F., Hamilton, S. R., Evans, D. B., Hooper, A. T., Pereira, D. S., Hicklin, D. J. & Ellis, L. M. (2007). Tyrosine kinase receptor RON in human pancreatic cancer: expression, function, and validation as a target. Cancer 109, 1030-1039. Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., Portillo, F. & Nieto, M. A. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2, 76-83. Chaffer, C. L. & Weinberg, R. A. (2011). A perspective on cancer cell metastasis. Science 331, 1559-1564. Chang, Y., Chang, S. S., Lee, H. H., Doong, S. L., Takada, K. & Tsai, C. H. (2004). Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference. J Gen Virol 85, 1371-1379. Chasserot-Golaz, S., Schuster, C., Dietrich, J. B., Beck, G. & Lawrence, D. A. (1988). Antagonistic action of RU38486 on the activity of transforming growth factor-beta in fibroblasts and lymphoma cells. J Steroid Biochem 30, 381-385. Chen, H., Lee, J. M., Zong, Y., Borowitz, M., Ng, M. H., Ambinder, R. F. & Hayward, S. D. (2001). Linkage between STAT regulation and Epstein-Barr virus gene expression in tumors. J Virol 75, 2929-2937. Chen, Q., Seol, D. W., Carr, B. & Zarnegar, R. (1997). Co-expression and regulation of Met and Ron proto-oncogenes in human hepatocellular carcinoma tissues and cell lines. Hepatology 26, 59-66. Chen, Y. Q., Zhou, Y. Q., Angeloni, D., Kurtz, A. L., Qiang, X. Z. & Wang, M. H. (2000). Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines. Exp Cell Res 261, 229-238. Chen, Y. Q., Zhou, Y. Q., Fu, L. H., Wang, D. & Wang, M. H. (2002). Multiple pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Recepteur d'origine nantais. Carcinogenesis 23, 1811-1819. Cheng, H. L., Liu, H. S., Lin, Y. J., Chen, H. H., Hsu, P. Y., Chang, T. Y., Ho, C. L., Tzai, T. S. & Chow, N. H. (2005). Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer 92, 1906-1914. Cheung, R. K. & Dosch, H. M. (1991). The tyrosine kinase lck is critically involved in the growth transformation of human B lymphocytes. J Biol Chem 266, 8667-8670. Chou, J., Lin, Y. C., Kim, J., You, L., Xu, Z., He, B. & Jablons, D. M. (2008). Nasopharyngeal carcinoma--review of the molecular mechanisms of tumorigenesis. Head Neck 30, 946-963. Cohen, J. I., Wang, F. & Kieff, E. (1991). Epstein-Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation. J Virol 65, 2545-2554. Cohen, J. I., Wang, F., Mannick, J. & Kieff, E. (1989). Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci U S A 86, 9558-9562. Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., Mareel, M., Huylebroeck, D. & van Roy, F. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 7, 1267-1278. Cote, M., Miller, A. D. & Liu, S. L. (2007). Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence. Biochem Biophys Res Commun 360, 219-225. Cottage, A., Clark, M., Hawker, K., Umrania, Y., Wheller, D., Bishop, M. & Elgar, G. (1999). Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes. FEBS Lett 443, 370-374. Countryman, J. & Miller, G. (1985). Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA. Proc Natl Acad Sci U S A 82, 4085-4089. Danilkovitch-Miagkova, A., Duh, F. M., Kuzmin, I., Angeloni, D., Liu, S. L., Miller, A. D. & Lerman, M. I. (2003). Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. Proc Natl Acad Sci U S A 100, 4580-4585. Danilkovitch-Miagkova, A., Miagkov, A., Skeel, A., Nakaigawa, N., Zbar, B. & Leonard, E. J. (2001). Oncogenic mutants of RON and MET receptor tyrosine kinases cause activation of the beta-catenin pathway. Mol Cell Biol 21, 5857-5868. Danilkovitch, A., Donley, S., Skeel, A. & Leonard, E. J. (2000). Two independent signaling pathways mediate the antiapoptotic action of macrophage-stimulating protein on epithelial cells. Mol Cell Biol 20, 2218-2227. Danilkovitch, A., Skeel, A. & Leonard, E. J. (1999). Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism. Exp Cell Res 248, 575-582. Dawson, C. W., Laverick, L., Morris, M. A., Tramoutanis, G. & Young, L. S. (2008). Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway. J Virol 82, 3654-3664. Dilworth, S. M. (1995). Polyoma virus middle T antigen: meddler or mimic? Trends Microbiol 3, 31-35. Dilworth, S. M. (2002). Polyoma virus middle T antigen and its role in identifying cancer-related molecules. Nat Rev Cancer 2, 951-956. Eder, J. P., Shapiro, G. I., Appleman, L. J., Zhu, A. X., Miles, D., Keer, H., Cancilla, B., Chu, F., Hitchcock-Bryan, S., Sherman, L., McCallum, S., Heath, E. I., Boerner, S. A. & LoRusso, P. M. (2010). A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2. Clin Cancer Res 16, 3507-3516. Eger, A., Aigner, K., Sonderegger, S., Dampier, B., Oehler, S., Schreiber, M., Berx, G., Cano, A., Beug, H. & Foisner, R. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 24, 2375-2385. Ellenberger, T., Fass, D., Arnaud, M. & Harrison, S. C. (1994). Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. Genes Dev 8, 970-980. Endo, K., Kondo, S., Shackleford, J., Horikawa, T., Kitagawa, N., Yoshizaki, T., Furukawa, M., Zen, Y. & Pagano, J. S. (2009). Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration. Oncogene 28, 1725-1735. Epstein, M. A., Achong, B. G. & Barr, Y. M. (1964). Virus Particles in Cultured Lymphoblasts from Burkitt's Lymphoma. Lancet 1, 702-703. Epstein, M. A., Achong, B. G., Barr, Y. M., Zajac, B., Henle, G. & Henle, W. (1966). Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji). J Natl Cancer Inst 37, 547-559. Epstein, M. A., Henle, G., Achong, B. G. & Barr, Y. M. (1965). Morphological and Biological Studies on a Virus in Cultured Lymphoblasts from Burkitt's Lymphoma. J Exp Med 121, 761-770. Faggioni, A., Zompetta, C., Grimaldi, S., Barile, G., Frati, L. & Lazdins, J. (1986). Calcium modulation activates Epstein-Barr virus genome in latently infected cells. Science 232, 1554-1556. Faqing, T., Zhi, H., Liqun, Y., Min, T., Huanhua, G., Xiyun, D. & Ya, C. (2005). Epstein-Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of Survivin in nasopharyngeal carcinoma. Exp Oncol 27, 96-101. Farina, A., Feederle, R., Raffa, S., Gonnella, R., Santarelli, R., Frati, L., Angeloni, A., Torrisi, M. R., Faggioni, A. & Delecluse, H. J. (2005). BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment and egress. J Virol 79, 3703-3712. Farrell, P. J. (1998). Signal transduction from the Epstein-Barr virus LMP-1 transforming protein. Trends Microbiol 6, 175-177; discussion 177-178. Feederle, R., Kost, M., Baumann, M., Janz, A., Drouet, E., Hammerschmidt, W. & Delecluse, H. J. (2000). The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. EMBO J 19, 3080-3089. Feres, K. J., Ischenko, I. & Hayman, M. J. (2009). The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells. Oncogene 28, 279-288. Fidler, I. J. (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 3, 453-458. Follenzi, A., Bakovic, S., Gual, P., Stella, M. C., Longati, P. & Comoglio, P. M. (2000). Cross-talk between the proto-oncogenes Met and Ron. Oncogene 19, 3041-3049. Fries, K. L., Miller, W. E. & Raab-Traub, N. (1996). Epstein-Barr virus latent membrane protein 1 blocks p53-mediated apoptosis through the induction of the A20 gene. J Virol 70, 8653-8659. Gaudino, G., Avantaggiato, V., Follenzi, A., Acampora, D., Simeone, A. & Comoglio, P. M. (1995). The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene 11, 2627-2637. Gaudino, G., Follenzi, A., Naldini, L., Collesi, C., Santoro, M., Gallo, K. A., Godowski, P. J. & Comoglio, P. M. (1994). RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. Embo J 13, 3524-3532. Gibbons, D. L., Rowe, M., Cope, A. P., Feldmann, M. & Brennan, F. M. (1994). Lymphotoxin acts as an autocrine growth factor for Epstein-Barr virus-transformed B cells and differentiated Burkitt lymphoma cell lines. Eur J Immunol 24, 1879-1885. Gires, O., Kohlhuber, F., Kilger, E., Baumann, M., Kieser, A., Kaiser, C., Zeidler, R., Scheffer, B., Ueffing, M. & Hammerschmidt, W. (1999). Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins. EMBO J 18, 3064-3073. Gires, O., Zimber-Strobl, U., Gonnella, R., Ueffing, M., Marschall, G., Zeidler, R., Pich, D. & Hammerschmidt, W. (1997). Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J 16, 6131-6140. Gong, M. & Kieff, E. (1990). Intracellular trafficking of two major Epstein-Barr virus glycoproteins, gp350/220 and gp110. J Virol 64, 1507-1516. Gruffat, H., Manet, E., Rigolet, A. & Sergeant, A. (1990). The enhancer factor R of Epstein-Barr virus (EBV) is a sequence-specific DNA binding protein. Nucleic Acids Res 18, 6835-6843. Haan, K. M., Kwok, W. W., Longnecker, R. & Speck, P. (2000). Epstein-Barr virus entry utilizing HLA-DP or HLA-DQ as a coreceptor. J Virol 74, 2451-2454. Hajra, K. M., Chen, D. Y. & Fearon, E. R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 62, 1613-1618. Hammerschmidt, W. & Sugden, B. (1989). Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes. Nature 340, 393-397. Han, S., Stuart, L. A. & Degen, S. J. (1991). Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry 30, 9768-9780. Harada, S. & Kieff, E. (1997). Epstein-Barr virus nuclear protein LP stimulates EBNA-2 acidic domain-mediated transcriptional activation. J Virol 71, 6611-6618. Hardwick, J. M., Lieberman, P. M. & Hayward, S. D. (1988). A new Epstein-Barr virus transactivator, R, induces expression of a cytoplasmic early antigen. J Virol 62, 2274-2284. Hemavathy, K., Ashraf, S. I. & Ip, Y. T. (2000). Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 257, 1-12. Henderson, S., Rowe, M., Gregory, C., Croom-Carter, D., Wang, F., Longnecker, R., Kieff, E. & Rickinson, A. (1991). Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65, 1107-1115. Henkel, T., Ling, P. D., Hayward, S. D. & Peterson, M. G. (1994). Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. Science 265, 92-95. Henle, W., Diehl, V., Kohn, G., Zur Hausen, H. & Henle, G. (1967). Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science 157, 1064-1065. Heslop, H. E. (2009). How I treat EBV lymphoproliferation. Blood 114, 4002-4008. Ho, C. H., Chen, C. L., Li, W. Y. & Chen, C. J. (2009). Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion. Carcinogenesis 30, 1443-1451. Horikawa, T., Sheen, T. S., Takeshita, H., Sato, H., Furukawa, M. & Yoshizaki, T. (2001). Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma. Am J Pathol 159, 27-33. Horikawa, T., Yoshizaki, T., Kondo, S., Furukawa, M., Kaizaki, Y. & Pagano, J. S. (2011). Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma. Br J Cancer 104, 1160-1167. Horikawa, T., Yoshizaki, T., Sheen, T. S., Lee, S. Y. & Furukawa, M. (2000). Association of latent membrane protein 1 and matrix metalloproteinase 9 with metastasis in nasopharyngeal carcinoma. Cancer 89, 715-723. Howe, J. G. & Steitz, J. A. (1986). Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc Natl Acad Sci U S A 83, 9006-9010. Hsieh, J. J. & Hayward, S. D. (1995). Masking of the CBF1/RBPJ kappa transcriptional repression domain by Epstein-Barr virus EBNA2. Science 268, 560-563. Hsu, M., Wu, S. Y., Chang, S. S., Su, I. J., Tsai, C. H., Lai, S. J., Shiau, A. L., Takada, K. & Chang, Y. (2008). Epstein-Barr virus lytic transactivator Zta enhances chemotactic activity through induction of interleukin-8 in nasopharyngeal carcinoma cells. J Virol 82, 3679-3688. Huang, Y. T., Liu, M. Y., Tsai, C. H. & Yeh, T. H. (2010). Upregulation of interleukin-1 by Epstein-Barr virus latent membrane protein 1 and its possible role in nasopharyngeal carcinoma cell growth. Head Neck 32, 869-876. Huen, D. S., Henderson, S. A., Croom-Carter, D. & Rowe, M. (1995). The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 10, 549-560. Huff, J. L., Jelinek, M. A., Borgman, C. A., Lansing, T. J. & Parsons, J. T. (1993). The protooncogene c-sea encodes a transmembrane protein-tyrosine kinase related to the Met/hepatocyte growth factor/scatter factor receptor. Proc Natl Acad Sci U S A 90, 6140-6144. Iwama, A., Okano, K., Sudo, T., Matsuda, Y. & Suda, T. (1994). Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells. Blood 83, 3160-3169. Iwama, A., Yamaguchi, N. & Suda, T. (1996). STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family. EMBO J 15, 5866-5875. Jat, P. & Arrand, J. R. (1982). In vitro transcription of two Epstein-Barr virus specified small RNA molecules. Nucleic Acids Res 10, 3407-3425. Javier, R. T. & Butel, J. S. (2008). The history of tumor virology. Cancer Res 68, 7693-7706. Johannsen, E., Koh, E., Mosialos, G., Tong, X., Kieff, E. & Grossman, S. R. (1995). Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1. J Virol 69, 253-262. Johannsen, E., Miller, C. L., Grossman, S. R. & Kieff, E. (1996). EBNA-2 and EBNA-3C extensively and mutually exclusively associate with RBPJkappa in Epstein-Barr virus-transformed B lymphocytes. J Virol 70, 4179-4183. Kang, Y. & Massague, J. (2004). Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118, 277-279. Kao, R. H., Huang, L. C. & Hsu, Y. H. (2002). Mapping the methylation pattern by bisulfite genomic sequencing of the E-cadherin promoter CpG island in nasopharyngeal carcinoma. Anticancer Res 22, 4109-4113. Kawanishi, M. (1997). Expression of Epstein-Barr virus latent membrane protein 1 protects Jurkat T cells from apoptosis induced by serum deprivation. Virology 228, 244-250. Kaye, K. M., Izumi, K. M. & Kieff, E. (1993). Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci U S A 90, 9150-9154. Kieff, E. & Rickinson, A. B. (2007). Epstein-Barr virus and its replication In Fields Virology, 5 edn, pp. 2603-2653. Edited by D. M. Knipe. & P. M. Howley: Lippincott Williams & Wilkins. Kienzle, N., Young, D., Silins, S. L. & Sculley, T. B. (1996). Induction of pleckstrin by the Epstein-Barr virus nuclear antigen 3 family. Virology 224, 167-174. Klatt, A., Zhang, Z., Kalantari, P., Hankey, P. A., Gilmour, D. S. & Henderson, A. J. (2008). The receptor tyrosine kinase RON represses HIV-1 transcription by targeting RNA polymerase II processivity. J Immunol 180, 1670-1677. Klein, E., Kis, L. L. & Klein, G. (2007). Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions. Oncogene 26, 1297-1305. Klein, S. C., Kube, D., Abts, H., Diehl, V. & Tesch, H. (1996). Promotion of IL8, IL10, TNF alpha and TNF beta production by EBV infection. Leuk Res 20, 633-636. Kondo, S., Wakisaka, N., Schell, M. J., Horikawa, T., Sheen, T. S., Sato, H., Furukawa, M., Pagano, J. S. & Yoshizaki, T. (2005). Epstein-Barr virus latent membrane protein 1 induces the matrix metalloproteinase-1 promoter via an Ets binding site formed by a single nucleotide polymorphism: enhanced susceptibility to nasopharyngeal carcinoma. Int J Cancer 115, 368-376. Kondo, S., Yoshizaki, T., Wakisaka, N., Horikawa, T., Murono, S., Jang, K. L., Joab, I., Furukawa, M. & Pagano, J. S. (2007). MUC1 induced by Epstein-Barr virus latent membrane protein 1 causes dissociation of the cell-matrix interaction and cellular invasiveness via STAT signaling. J Virol 81, 1554-1562. Kudoh, A., Daikoku, T., Ishimi, Y., Kawaguchi, Y., Shirata, N., Iwahori, S., Isomura, H. & Tsurumi, T. (2006). Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication. J Virol 80, 10064-10072. Kudoh, A., Daikoku, T., Sugaya, Y., Isomura, H., Fujita, M., Kiyono, T., Nishiyama, Y. & Tsurumi, T. (2004). Inhibition of S-phase cyclin-dependent kinase activity blocks expression of Epstein-Barr virus immediate-early and early genes, preventing viral lytic replication. J Virol 78, 104-115. Kudoh, A., Fujita, M., Kiyono, T., Kuzushima, K., Sugaya, Y., Izuta, S., Nishiyama, Y. & Tsurumi, T. (2003). Reactivation of lytic replication from B cells latently infected with Epstein-Barr virus occurs with high S-phase cyclin-dependent kinase activity while inhibiting cellular DNA replication. J Virol 77, 851-861. Kulwichit, W., Edwards, R. H., Davenport, E. M., Baskar, J. F., Godfrey, V. & Raab-Traub, N. (1998). Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci U S A 95, 11963-11968. Kung, C. P., Meckes, D. G., Jr. & Raab-Traub, N. (2011). Epstein-Barr virus LMP1 activates EGFR, STAT3, and ERK through effects on PKCdelta. J Virol 85, 4399-4408. Kung, C. P. & Raab-Traub, N. (2008). Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor through effects on Bcl-3 and STAT3. J Virol 82, 5486-5493. Kung, C. P. & Raab-Traub, N. (2010). Epstein-Barr virus latent membrane protein 1 modulates distinctive NF- kappaB pathways through C-terminus-activating region 1 to regulate epidermal growth factor receptor expression. J Virol 84, 6605-6614. Kung, H. J., Chen, H. C. & Robinson, D. (1998). Molecular profiling of tyrosine kinases in normal and cancer cells. J Biomed Sci 5, 74-78. Kuppers, R. (2003). B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol 3, 801-812. Kurihara, N., Iwama, A., Tatsumi, J., Ikeda, K. & Suda, T. (1996). Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. Blood 87, 3704-3710. Kutz, H., Reisbach, G., Schultheiss, U. & Kieser, A. (2008). The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus. Virology 371, 246-256. Lee, M. A., Diamond, M. E. & Yates, J. L. (1999). Genetic evidence that EBNA-1 is needed for efficient, stable latent infection by Epstein-Barr virus. J Virol 73, 2974-2982. Leonis, M. A., Toney-Earley, K., Degen, S. J. & Waltz, S. E. (2002). Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure. Hepatology 36, 1053-1060. Li, B. Q., Wang, M. H., Kung, H. F., Ronsin, C., Breathnach, R., Leonard, E. J. & Kamata, T. (1995a). Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor. Biochem Biophys Res Commun 216, 110-118. Li, H. P. & Chang, Y. S. (2003). Epstein-Barr virus latent membrane protein 1: structure and functions. J Biomed Sci 10, 490-504. Li, J. S., Zhou, B. S., Dutschman, G. E., Grill, S. P., Tan, R. S. & Cheng, Y. C. (1987). Association of Epstein-Barr virus early antigen diffuse component and virus-specified DNA polymerase activity. J Virol 61, 2947-2949. Li, Q., Spriggs, M. K., Kovats, S., Turk, S. M., Comeau, M. R., Nepom, B. & Hutt-Fletcher, L. M. (1997). Epstein-Barr virus uses HLA class II as a cofactor for infection of B lymphocytes. J Virol 71, 4657-4662. Li, Q., Turk, S. M. & Hutt-Fletcher, L. M. (1995b). The Epstein-Barr virus (EBV) BZLF2 gene product associates with the gH and gL homologs of EBV and carries an epitope critical to infection of B cells but not of epithelial cells. J Virol 69, 3987-3994. Li, Y., Mahajan, N. P., Webster-Cyriaque, J., Bhende, P., Hong, G. K., Earp, H. S. & Kenney, S. (2004). The C-mer gene is induced by Epstein-Barr virus immediate-early protein BRLF1. J Virol 78, 11778-11785. Lin, C. T., Chan, W. Y., Chen, W., Huang, H. M., Wu, H. C., Hsu, M. M., Chuang, S. M. & Wang, C. C. (1993). Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest 68, 716-727. Lin, H. S., Berry, G. J., Fee, W. E., Jr., Terris, D. J. & Sun, Z. (2004). Identification of tyrosine kinases overexpressed in head and neck cancer. Arch Otolaryngol Head Neck Surg 130, 311-316. Lin, J. C., Shaw, J. E., Smith, M. C. & Pagano, J. S. (1979). Effect of 12-O-tetradecanoyl-phorbol-13-acetate on the replication of Epstein-Barr virus. I. Characterization of viral DNA. Virology 99, 183-187. Lin, J. C., Sista, N. D., Besencon, F., Kamine, J. & Pagano, J. S. (1991). Identification and functional characterization of Epstein-Barr virus DNA polymerase by in vitro transcription-translation of a cloned gene. J Virol 65, 2728-2731. Lin, J. H., Tsai, C. H., Chu, J. S., Chen, J. Y., Takada, K. & Shew, J. Y. (2007). Dysregulation of HER2/HER3 signaling axis in Epstein-Barr virus-infected breast carcinoma cells. J Virol 81, 5705-5713. Liu, M. T., Chang, Y. T., Chen, S. C., Chuang, Y. C., Chen, Y. R., Lin, C. S. & Chen, J. Y. (2005). Epstein-Barr virus latent membrane protein 1 represses p53-mediated DNA repair and transcriptional activity. Oncogene 24, 2635-2646. Liu, M. T., Chen, Y. R., Chen, S. C., Hu, C. Y., Lin, C. S., Chang, Y. T., Wang, W. B. & Chen, J. Y. (2004). Epstein-Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells. Oncogene 23, 2531-2539. Liu, P. & Speck, S. H. (2003). Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and Zta. Virology 310, 199-206. Liu, R., Gong, M., Li, X., Zhou, Y., Gao, W., Tulpule, A., Chaudhary, P. M., Jung, J. & Gill, P. S. (2010). Induction, regulation, and biologic function of Axl receptor tyrosine kinase in Kaposi sarcoma. Blood 116, 297-305. Liu, S. L. & Miller, A. D. (2007). Oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein. Oncogene 26, 789-801. Lo, K. W., To, K. F. & Huang, D. P. (2004). Focus on nasopharyngeal carcinoma. Cancer Cell 5, 423-428. Logan-Collins, J., Thomas, R. M., Yu, P., Jaquish, D., Mose, E., French, R., Stuart, W., McClaine, R., Aronow, B., Hoffman, R. M., Waltz, S. E. & Lowy, A. M. (2010). Silencing of RON receptor signaling promotes apoptosis and gemcitabine sensitivity in pancreatic cancers. Cancer Res 70, 1130-1140. Lu, J., Chen, S. Y., Chua, H. H., Liu, Y. S., Huang, Y. T., Chang, Y., Chen, J. Y., Sheen, T. S. & Tsai, C. H. (2000). Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta. J Virol 74, 7391-7399. Lu, J., Lin, W. H., Chen, S. Y., Longnecker, R., Tsai, S. C., Chen, C. L. & Tsai, C. H. (2006). Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. J Biol Chem 281, 8806-8814. Luka, J., Kallin, B. & Klein, G. (1979). Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate. Virology 94, 228-231. Maggiora, P., Lorenzato, A., Fracchioli, S., Costa, B., Castagnaro, M., Arisio, R., Katsaros, D., Massobrio, M., Comoglio, P. M. & Flavia Di Renzo, M. (2003). The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 288, 382-389. Maggiora, P., Marchio, S., Stella, M. C., Giai, M., Belfiore, A., De Bortoli, M., Di Renzo, M. F., Costantino, A., Sismondi, P. & Comoglio, P. M. (1998). Overexpression of the RON gene in human breast carcinoma. Oncogene 16, 2927-2933. Mannick, J. B., Cohen, J. I., Birkenbach, M., Marchini, A. & Kieff, E. (1991). The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation. J Virol 65, 6826-6837. Marshall, D. & Sample, C. (1995). Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator. J Virol 69, 3624-3630. Martin, G. S. (2001). The hunting of the Src. Nat Rev Mol Cell Biol 2, 467-475. Massari, M. E. & Murre, C. (2000). Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20, 429-440. Mauser, A., Holley-Guthrie, E., Zanation, A., Yarborough, W., Kaufmann, W., Klingelhutz, A., Seaman, W. T. & Kenney, S. (2002). The Epstein-Barr virus immediate-early protein BZLF1 induces expression of E2F-1 and other proteins involved in cell cycle progression in primary keratinocytes and gastric carcinoma cells. J Virol 76, 12543-12552. McClaine, R. J., Marshall, A. M., Wagh, P. K. & Waltz, S. E. (2010). Ron receptor tyrosine kinase activation confers resistance to tamoxifen in breast cancer cell lines. Neoplasia 12, 650-658. McDowell, S. A., Mallakin, A., Bachurski, C. J., Toney-Earley, K., Prows, D. R., Bruno, T., Kaestner, K. H., Witte, D. P., Melin-Aldana, H., Degen, S. J., Leikauf, G. D. & Waltz, S. E. (2002). The role of the receptor tyrosine kinase Ron in nickel-induced acute lung injury. Am J Respir Cell Mol Biol 26, 99-104. Medico, E., Mongiovi, A. M., Huff, J., Jelinek, M. A., Follenzi, A., Gaudino, G., Parsons, J. T. & Comoglio, P. M. (1996). The tyrosine kinase receptors Ron and Sea control 'scattering' and morphogenesis of liver progenitor cells in vitro. Mol Biol Cell 7, 495-504. Mettenleiter, T. C. (2004). Budding events in herpesvirus morphogenesis. Virus Res 106, 167-180. Miller, N. & Hutt-Fletcher, L. M. (1988). A monoclonal antibody to glycoprotein gp85 inhibits fusion but not attachment of Epstein-Barr virus. J Virol 62, 2366-2372. Miller, W. E., Earp, H. S. & Raab-Traub, N. (1995). The Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor. J Virol 69, 4390-4398. Morabito, C. J., Dettman, R. W., Kattan, J., Collier, J. M. & Bristow, J. (2001). Positive and negative regulation of epicardial-mesenchymal transformation during avian heart development. Dev Biol 234, 204-215. Morris, J. D., Eddleston, A. L. & Crook, T. (1995). Viral infection and cancer. Lancet 346, 754-758. Muraoka, R. S., Sun, W. Y., Colbert, M. C., Waltz, S. E., Witte, D. P., Degen, J. L. & Friezner Degen, S. J. (1999). The Ron/STK receptor tyrosine kinase is essential for peri-implantation development in the mouse. J Clin Invest 103, 1277-1285. Murono, S., Inoue, H., Tanabe, T., Joab, I., Yoshizaki, T., Furukawa, M. & Pagano, J. S. (2001). Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A 98, 6905-6910. Nakamura, T., Aoki, S., Takahashi, T., Matsumoto, K. & Kiyohara, T. (1996). Cloning and expression of Xenopus HGF-like protein (HLP) and Ron/HLP receptor implicate their involvement in early neural development. Biochem Biophys Res Commun 224, 564-573. Nalesnik, | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23648 | - |
dc.description.abstract | EB病毒是一具致癌性的疱疹病毒,與許多惡性疾病有高度相關,包含Burkitt 氏淋巴瘤、Hodgkin氏症、T細胞淋巴瘤、NK細胞淋巴瘤、移植後淋巴增生疾病及鼻咽癌。EB病毒可以透過多種調控機制不朽化(immortalize)人類初代B細胞轉形為具有不斷分裂能力的淋巴母細胞株(LCL)。然而,對於酪胺酸激酶在EB病毒所造成的B細胞不斷增生的關係尚不清楚。在此研究中,我們利用kinase display方法發現RON酪胺酸激酶會表現在淋巴母細胞株中,但不表現在正常的B淋巴球中。進一步,我們發現在B細胞株及淋巴母細胞株中均可觀察到EB病毒所表現的潛伏膜蛋白1 (LMP1)可以直接透過其上的CTAR1 domain活化NF-kB結合到RON之啟動子上,而增加RON的表現及活化其酪胺酸激酶的活性。剔除RON的表現就可成功地抑制淋巴母細胞株的生長,而在LMP1剔除的細胞中,表現RON則可以回復剔除LMP1所造成的生長抑制。免疫組織化學分析發現移植後淋巴增生性疾病病人的切片檢體可以觀察到LMP1和RON的表現具有相關性,証實LMP1所誘導之RON不僅為影響淋巴母細胞株生長所必需而且RON在移植後淋巴增生疾病的致病機轉中扮演重要角色。
另一方面,鼻咽癌不同於其他頭頸部的癌症是因為具有高度的轉移性且和EB病毒有高度相關性。我們發現LMP1可以誘導RON表現並活化其酪胺酸激酶活性而刺激上皮間質細胞轉化epithelial- mesenchymal transition (EMT)和促進細胞移動及入侵。此外,ERK為LMP1和RON下游之訊息傳遞鏈的重要分子。剔除RON可以回復LMP1所誘導的上皮間質細胞轉化和抑制LMP1所引起的細胞移動及入侵和抑制ERK的活化。在分子機制方面,可以觀察到LMP1透過其CTAR1 domain活化NF-kB結合到RON之啟動子而促進RON表現。免疫組織化學染色顯示RON大量表現在原位鼻咽癌和轉移鼻咽癌的病人檢體中而不表現在控制組組織,而且LMP1和RON的表現有顯著的相關性。 這些結果提供RON在移植後淋巴增生性疾病及鼻咽癌的致病機轉中的新觀點,推測RON可能可以成為在EB病毒相關疾病中新穎的治療標靶分子。 | zh_TW |
dc.description.abstract | Epstein-Barr virus (EBV), an oncogenic human herpesvirus, is associated with several malignancies, including Burkitt’s lymphoma, Hodgkin’s lymphoma, T cell lymphoma, NK cell lymphoma, post-transplantation lymphoproliferative disorder (PTLD), and nasopharyngeal carcinoma (NPC). EBV can transform primary B lymphocytes into immortalized lymphoblastoid cell lines (LCLs) through multiple regulatory mechanisms. However, the involvement of protein tyrosine kinases in the infinite proliferation of B cells is not clear. In this study, we performed kinase display assays to investigate this subject and identified a specific cellular target, Recepteur d’Origine Nantais (RON) tyrosine kinase, expressed in LCLs but not in primary B cells. Furthermore, we found that latent membrane protein 1 (LMP1), an important EBV oncogenic protein, enhanced RON expression and activation through its carboxyl-terminal activation region-1 (CTAR1) by promoting nuclear factor (NF)-kB binding to the RON promoter in B cells and LCLs. RON knockdown decreased the proliferation of LCLs and transfection with RON compensated for the growth inhibition caused by knockdown of LMP1. Immunohistochemical analysis revealed a correlation between LMP1 and RON expression in biopsies from PTLD, suggesting that LMP1-induced RON expression not only is essential for the growth of LCLs but also may contribute to the pathogenesis of EBV-associated PTLD.
In addition, NPC is distinct from other human head and neck cancers because of its highly metastatic character and strong association with EBV. Here we show that the LMP1 induces and activates RON to stimulate epithelial-mesenchymal transition (EMT) and promotes cell migration and invasion. Furthermore, ERK is known to be involved in the downstream signaling of LMP1-RON pathways. Knockdown of RON in cells expressing LMP1 significantly reverses LMP1-induced EMT, suppresses LMP1-induced cell migration and invasion, and inhibits ERK activation. At the molecular level, LMP1 stimulates NF-kB binding to the RON promoter through its CTAR1 domain to induce expression of RON. Immunohistochemical staining showed expression of RON in NPC biopsies but not in control tissues and revealed a significant correlation of LMP1 and RON expression in biopsies from primary and metastatic NPC. These results may provide a new insight into the pathogenesis of RON receptor tyrosine kinase in PTLD and NPC, suggesting that RON may be a novel therapeutic target for EBV-associated diseases. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:06:44Z (GMT). No. of bitstreams: 1 ntu-100-D94445003-1.pdf: 4127002 bytes, checksum: 5f7bd53f30a80a217f4a27a9a43eca90 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書……………………………………………………. i
中文摘要………………………………………………………………. ii 英文摘要………………………………………………………………. iii Contents………………………………………………………………... iv 1. Introduction …………………………………………………………...1 1.1 Discovery, characteristics, and genome of EBV ………………...1 1.2 Prospected route of EBV infection…………………………….....2 1.3 Life cycle of EBV………………………………………………...3 1.4 Latent gene products of EBV………………………………….....5 1.5 Latent membrane protein 1 (LMP1)…………………………….. 7 1.6 Lytic gene products of EBV…………………………………….. 8 1.7 EBV-associated diseases………………………………………… 9 1.8 Viral infection and tumor………………………………………. 10 1.9 Viral infection and tyrosine kinase……………………………. 10 1.10 Recepteur d’Origine Nantais (RON)…………………………... 12 1.10.1 Discovery and characteristics of RON…………………… 12 1.10.2 Expression profiles of RON……………………………….13 1.10.3 Regulation of RON………………………………………...14 1.10.4 Biological functions of RON………………………………15 1.11 Epithelial-mesenchymal transition (EMT)……………………..17 1.11.1 Discovery and characteristics of EMT…………………….17 1.11.2 Regulation of EMT………………………………………...18 1.11.3 EMT and tumor metastasis………………………………...18 1.12 Aims of this study………………………………………….......19 2. Materials and method …………………………………………………21 2.1 Preparation of EBV virion ……………………………………….21 2.2 B cells purification and EBV infection ………………………….21 2.3 Flow cytometry analysis …………………………………………22 2.4 Cell culture ……………………………………………………….22 2.5 Plasmids ………………………………………………………….23 2.6 Electroporation …………………………………………………..24 2.7 Preparation and infection of LMP1 and shLMP1 expressing lentiviruses …………………………………………25 2.8 RNA extraction, reverse transcription and quantitative polymerase chain reaction (RT-Q-PCR) ………………….……..25 2.9 Western blotting …………………………………………………26 2.10 Antibodies…………….…………………………………………27 2.11 Immunoprecipitation assay …………………………………….27 2.12 in vitro RON kinase assay ……………………………………...28 2.13 Treatment with NF-kB inhibitor ………………………………..29 2.14 Chromatin immunoprecipitation (ChIP) assay ………………….29 2.15 [3H]-thymidine incorporation assay for cell proliferation ………31 2.16 Treatment with signal pathway inhibitors ………………………31 2.17 Observation of morphological changes and immunofluorescence staining………………………………….31 2.18 Wound healing assay ……………………………………………32 2.19 Transwell migration and matrigel invasion assay ………………32 2.20 Biopsy samples ………………………………………. ………33 2.21 Immunohistochemistry (IHC) assay …………………………..33 2.22 in situ Hybridization Assay for EBER ………………………...33 2.23 Co-immunoprecipitation assay …………………………………34 2.24 Statistic analysis ………………………………………………..34 3. Results…………………………………………………………………35 3.1 Expression of RON is induced in LCLs by EBV infection ……35 3.2 EBV-induced expression of RON is triggered by LMP1 ………36 3.3 The phosphorylation status of RON is increased in LMP1 expressing cells……………………………………36 3.4 LMP1 regulates RON expression through CTAR1 domain ………37 3.5 LMP1 induces RON expression through NF-kB pathway..………38 3.6 LMP1 induces p65 directly binds to RON promoter ……………38 3.7 LMP1-induced RON expression is required for growth of LCLs ………………………………………………………38 3.8 The downstream signaling pathways are triggered by RON in LCLs …………………………………………………39 3.9 The downstream signaling pathways of RON affect LCLs Proliferation……………………………………………39 3.10 RON expression is detectable in biopsies of PTLD …………40 3.11 RON plays a pivotal role in LMP1-mediated cell morphological changes and EMT ……………………………40 3.12 LMP1-induced RON expression triggers cell migration and invasion ………………………………………………42 3.13 ERK activation, induced by LMP1 through RON, is important for LMP1-induced migration and invasion ………42 3.14 Expression of LMP1 and RON is highly correlated in primary and metastatic NPC biopsies.………………………43 4. Discussion……………………………………………………………44 4.1 The tyrosine kinases induced by EBV…………………………44 4.2 The regulatory mechanism of LMP1-induced RON expression………………………………………………………45 4.3 The downstream signaling pathways of RON affected LMP1-mediated cellular function………………………46 4.4 The association of RON and virus………………………………47 4.5 The LMP1-induced RON expression in EMT process…………48 4.6 The role of RON in EBV-associated diseases………………49 4.7 The clinical implication of RON in EBV-associated diseases……50 4.8 Conclusion……………………………………………………51 | |
dc.language.iso | en | |
dc.title | 探查EB病毒感染中RON 酪胺酸激酶的表現及其對EB病毒相關疾病的致病機轉之影響 | zh_TW |
dc.title | Expression of RON receptor tyrosine kinase in Epstein-Barr virus infection and its impact on the pathogenesis of
EBV-associated diseases | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 陳紀如,林素珍,呂仁,李明學 | |
dc.subject.keyword | RON酪胺酸激酶,EB病毒,淋巴母細胞株,潛伏膜蛋白1,移植後淋巴增生疾病,上皮間質細胞轉化,鼻咽癌, | zh_TW |
dc.subject.keyword | RON (Recepteur d’Origine Nantais),Epstein-Barr virus (EBV),lymphoblastoid cell lines (LCLs),latent membrane protein 1 (LMP1),post-transplantation lymphoproliferative disorder (PTLD),Epithelial-Mesenchymal Transition (EMT),nasopharyngeal carcinoma (NPC), | en |
dc.relation.page | 110 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-06-30 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-100-1.pdf 目前未授權公開取用 | 4.03 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。