請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5188完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 康照洲(Jaw-Jou Kang) | |
| dc.contributor.author | Wen-Hao Yang | en |
| dc.contributor.author | 楊文豪 | zh_TW |
| dc.date.accessioned | 2021-05-15T17:53:13Z | - |
| dc.date.available | 2017-03-12 | |
| dc.date.available | 2021-05-15T17:53:13Z | - |
| dc.date.copyright | 2015-03-12 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-12-01 | |
| dc.identifier.citation | Abdelrahim, M., Smith, R., 3rd, and Safe, S. (2003). Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Molecular pharmacology 63, 1373-1381.
Adachi, J., Mori, Y., Matsui, S., Takigami, H., Fujino, J., Kitagawa, H., Miller, C.A., 3rd, Kato, T., Saeki, K., and Matsuda, T. (2001). Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. The Journal of biological chemistry 276, 31475-31478. Andreola, F., Fernandez-Salguero, P.M., Chiantore, M.V., Petkovich, M.P., Gonzalez, F.J., and De Luca, L.M. (1997). Aryl hydrocarbon receptor knockout mice (AHR-/-) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. Cancer research 57, 2835-2838. Arora, K., and Warrior, R. (2001). A new Smurf in the village. Developmental cell 1, 441-442. Baba, T., Mimura, J., Nakamura, N., Harada, N., Yamamoto, M., Morohashi, K., and Fujii-Kuriyama, Y. (2005). Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Molecular and cellular biology 25, 10040-10051. Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A.A., Kim, S., Wilson, C.J., Lehar, J., Kryukov, G.V., Sonkin, D., et al. (2012). The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603-607. Belguise, K., Guo, S., Yang, S., Rogers, A.E., Seldin, D.C., Sherr, D.H., and Sonenshein, G.E. (2007). Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the aryl hydrocarbon receptor, slug, and an invasive phenotype. Cancer research 67, 11742-11750. Bhat-Nakshatri, P., Appaiah, H., Ballas, C., Pick-Franke, P., Goulet, R., Jr., Badve, S., Srour, E.F., and Nakshatri, H. (2010). SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24- phenotype. BMC cancer 10, 411. Bhowmick, N.A., Ghiassi, M., Bakin, A., Aakre, M., Lundquist, C.A., Engel, M.E., Arteaga, C.L., and Moses, H.L. (2001). Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Molecular biology of the cell 12, 27-36. Bierie, B., and Moses, H.L. (2006). Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nature reviews Cancer 6, 506-520. Bonni, S., Wang, H.R., Causing, C.G., Kavsak, P., Stroschein, S.L., Luo, K., and Wrana, J.L. (2001). TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nature cell biology 3, 587-595. Bracken, C.P., Gregory, P.A., Kolesnikoff, N., Bert, A.G., Wang, J., Shannon, M.F., and Goodall, G.J. (2008). A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer research 68, 7846-7854. Butler, R., Inzunza, J., Suzuki, H., Fujii-Kuriyama, Y., Warner, M., and Gustafsson, J.A. (2012). Uric acid stones in the urinary bladder of aryl hydrocarbon receptor (AhR) knockout mice. Proceedings of the National Academy of Sciences of the United States of America 109, 1122-1126. Carvajal-Gonzalez, J.M., Roman, A.C., Cerezo-Guisado, M.I., Rico-Leo, E.M., Martin-Partido, G., and Fernandez-Salguero, P.M. (2009). Loss of dioxin-receptor expression accelerates wound healing in vivo by a mechanism involving TGFbeta. Journal of cell science 122, 1823-1833. Casado, F.L., Singh, K.P., and Gasiewicz, T.A. (2011). Aryl hydrocarbon receptor activation in hematopoietic stem/progenitor cells alters cell function and pathway-specific gene modulation reflecting changes in cellular trafficking and migration. Molecular pharmacology 80, 673-682. Chang, X., Fan, Y., Karyala, S., Schwemberger, S., Tomlinson, C.R., Sartor, M.A., and Puga, A. (2007). Ligand-independent regulation of transforming growth factor beta1 expression and cell cycle progression by the aryl hydrocarbon receptor. Molecular and cellular biology 27, 6127-6139. Chaudhury, A., Hussey, G.S., Ray, P.S., Jin, G., Fox, P.L., and Howe, P.H. (2010). TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nature cell biology 12, 286-293. Chevallier, A., Mialot, A., Petit, J.M., Fernandez-Salguero, P., Barouki, R., Coumoul, X., and Beraneck, M. (2013). Oculomotor deficits in aryl hydrocarbon receptor null mouse. PloS one 8, e53520. Chiang, A.C., and Massague, J. (2008). Molecular basis of metastasis. The New England journal of medicine 359, 2814-2823. Choy, L., Skillington, J., and Derynck, R. (2000). Roles of autocrine TGF-beta receptor and Smad signaling in adipocyte differentiation. The Journal of cell biology 149, 667-682. Chuang, C.Y., Chang, H., Lin, P., Sun, S.J., Chen, P.H., Lin, Y.Y., Sheu, G.T., Ko, J.L., Hsu, S.L., and Chang, J.T. (2012). Up-regulation of osteopontin expression by aryl hydrocarbon receptor via both ligand-dependent and ligand-independent pathways in lung cancer. Gene 492, 262-269. Ciechanover, A., Hargrove, J.L., and Gross-Mesilaty, S. (1997). Ubiquitin-mediated degradation of tyrosine aminotransferase (TAT) in vitro and in vivo. Molecular biology reports 24, 27-33. Cocolakis, E., Lemay, S., Ali, S., and Lebrun, J.J. (2001). The p38 MAPK pathway is required for cell growth inhibition of human breast cancer cells in response to activin. The Journal of biological chemistry 276, 18430-18436. Coffey, R.J., Jr., Sipes, N.J., Bascom, C.C., Graves-Deal, R., Pennington, C.Y., Weissman, B.E., and Moses, H.L. (1988). Growth modulation of mouse keratinocytes by transforming growth factors. Cancer research 48, 1596-1602. Cox, M.B., and Miller, C.A., 3rd (2004). Cooperation of heat shock protein 90 and p23 in aryl hydrocarbon receptor signaling. Cell stress & chaperones 9, 4-20. Davies, M., Robinson, M., Smith, E., Huntley, S., Prime, S., and Paterson, I. (2005). Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways. Journal of cellular biochemistry 95, 918-931. de Guise, C., Lacerte, A., Rafiei, S., Reynaud, R., Roy, M., Brue, T., and Lebrun, J.J. (2006). Activin inhibits the human Pit-1 gene promoter through the p38 kinase pathway in a Smad-independent manner. Endocrinology 147, 4351-4362. de Herreros, A.G., Peiro, S., Nassour, M., and Savagner, P. (2010). Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. Journal of mammary gland biology and neoplasia 15, 135-147. Derynck, R., Akhurst, R.J., and Balmain, A. (2001). TGF-beta signaling in tumor suppression and cancer progression. Nature genetics 29, 117-129. Derynck, R., and Zhang, Y.E. (2003). Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425, 577-584. Dever, D.P., and Opanashuk, L.A. (2012). The aryl hydrocarbon receptor contributes to the proliferation of human medulloblastoma cells. Molecular pharmacology 81, 669-678. Dietrich, C., and Kaina, B. (2010). The aryl hydrocarbon receptor (AhR) in the regulation of cell-cell contact and tumor growth. Carcinogenesis 31, 1319-1328. Dohr, O., Sinning, R., Vogel, C., Munzel, P., and Abel, J. (1997). Effect of transforming growth factor-beta1 on expression of aryl hydrocarbon receptor and genes of Ah gene battery: clues for independent down-regulation in A549 cells. Molecular pharmacology 51, 703-710. Edlund, S., Landstrom, M., Heldin, C.H., and Aspenstrom, P. (2002). Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Molecular biology of the cell 13, 902-914. Fan, Y., Boivin, G.P., Knudsen, E.S., Nebert, D.W., Xia, Y., and Puga, A. (2010). The aryl hydrocarbon receptor functions as a tumor suppressor of liver carcinogenesis. Cancer research 70, 212-220. Fukuchi, M., Imamura, T., Chiba, T., Ebisawa, T., Kawabata, M., Tanaka, K., and Miyazono, K. (2001). Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins. Molecular biology of the cell 12, 1431-1443. Fukunaga, B.N., Probst, M.R., Reisz-Porszasz, S., and Hankinson, O. (1995). Identification of functional domains of the aryl hydrocarbon receptor. The Journal of biological chemistry 270, 29270-29278. Gomez-Duran, A., Mulero-Navarro, S., Chang, X., and Fernandez-Salguero, P.M. (2006). LTBP-1 blockade in dioxin receptor-null mouse embryo fibroblasts decreases TGF-beta activity: Role of extracellular proteases plasmin and elastase. Journal of cellular biochemistry 97, 380-392. Gomis, R.R., Alarcon, C., He, W., Wang, Q., Seoane, J., Lash, A., and Massague, J. (2006). A FoxO-Smad synexpression group in human keratinocytes. Proceedings of the National Academy of Sciences of the United States of America 103, 12747-12752. Gonzalez, F.J. (2005). Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutation research 569, 101-110. Graff, J.R., Gabrielson, E., Fujii, H., Baylin, S.B., and Herman, J.G. (2000). Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. The Journal of biological chemistry 275, 2727-2732. Gramatzki, D., Pantazis, G., Schittenhelm, J., Tabatabai, G., Kohle, C., Wick, W., Schwarz, M., Weller, M., and Tritschler, I. (2009). Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells. Oncogene 28, 2593-2605. Hemavathy, K., Ashraf, S.I., and Ip, Y.T. (2000). Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 257, 1-12. Hussey, G.S., Chaudhury, A., Dawson, A.E., Lindner, D.J., Knudsen, C.R., Wilce, M.C., Merrick, W.C., and Howe, P.H. (2011). Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Molecular cell 41, 419-431. Ikushima, H., Komuro, A., Isogaya, K., Shinozaki, M., Hellman, U., Miyazawa, K., and Miyazono, K. (2008). An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-beta signalling. The EMBO journal 27, 2955-2965. Ikuta, T., and Kawajiri, K. (2006). Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor. Experimental cell research 312, 3585-3594. Imamura, T., Takase, M., Nishihara, A., Oeda, E., Hanai, J., Kawabata, M., and Miyazono, K. (1997). Smad6 inhibits signalling by the TGF-beta superfamily. Nature 389, 622-626. Itoh, S., Itoh, F., Goumans, M.J., and Ten Dijke, P. (2000). Signaling of transforming growth factor-beta family members through Smad proteins. European journal of biochemistry / FEBS 267, 6954-6967. Kalthoff, S., Ehmer, U., Freiberg, N., Manns, M.P., and Strassburg, C.P. (2010). Coffee induces expression of glucuronosyltransferases by the aryl hydrocarbon receptor and Nrf2 in liver and stomach. Gastroenterology 139, 1699-1710, 1710 e1691-1692. Kawajiri, K., Kobayashi, Y., Ohtake, F., Ikuta, T., Matsushima, Y., Mimura, J., Pettersson, S., Pollenz, R.S., Sakaki, T., Hirokawa, T., et al. (2009). Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands. Proceedings of the National Academy of Sciences of the United States of America 106, 13481-13486. Kekatpure, V.D., Dannenberg, A.J., and Subbaramaiah, K. (2009). HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl hydrocarbon receptor signaling. The Journal of biological chemistry 284, 7436-7445. Kong, A.P., Xiao, K., Choi, K.C., Wang, G., Chan, M.H., Ho, C.S., Chan, I., Wong, C.K., Chan, J.C., and Szeto, C.C. (2012). Associations between microRNA (miR-21, 126, 155 and 221), albuminuria and heavy metals in Hong Kong Chinese adolescents. Clinica chimica acta; international journal of clinical chemistry 413, 1053-1057. Kurrey, N.K., Jalgaonkar, S.P., Joglekar, A.V., Ghanate, A.D., Chaskar, P.D., Doiphode, R.Y., and Bapat, S.A. (2009). Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem cells 27, 2059-2068. Lahvis, G.P., Lindell, S.L., Thomas, R.S., McCuskey, R.S., Murphy, C., Glover, E., Bentz, M., Southard, J., and Bradfield, C.A. (2000). Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 97, 10442-10447. Lahvis, G.P., Pyzalski, R.W., Glover, E., Pitot, H.C., McElwee, M.K., and Bradfield, C.A. (2005). The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Molecular pharmacology 67, 714-720. Lamouille, S., Connolly, E., Smyth, J.W., Akhurst, R.J., and Derynck, R. (2012). TGF-beta-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. Journal of cell science 125, 1259-1273. Lamouille, S., and Derynck, R. (2007). Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. The Journal of cell biology 178, 437-451. Lander, R., Nordin, K., and LaBonne, C. (2011). The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1. The Journal of cell biology 194, 17-25. Lee, M.K., Pardoux, C., Hall, M.C., Lee, P.S., Warburton, D., Qing, J., Smith, S.M., and Derynck, R. (2007). TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. The EMBO journal 26, 3957-3967. Lee, P.S., Chang, C., Liu, D., and Derynck, R. (2003). Sumoylation of Smad4, the common Smad mediator of transforming growth factor-beta family signaling. The Journal of biological chemistry 278, 27853-27863. Levy, L., and Hill, C.S. (2006). Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine & growth factor reviews 17, 41-58. Lo, R.S., and Massague, J. (1999). Ubiquitin-dependent degradation of TGF-beta-activated smad2. Nature cell biology 1, 472-478. Lund, A.K., Goens, M.B., Kanagy, N.L., and Walker, M.K. (2003). Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure. Toxicology and applied pharmacology 193, 177-187. Lund, A.K., Goens, M.B., Nunez, B.A., and Walker, M.K. (2006). Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice. Toxicology and applied pharmacology 212, 127-135. Ma, Q., and Whitlock, J.P., Jr. (1996). The aromatic hydrocarbon receptor modulates the Hepa 1c1c7 cell cycle and differentiated state independently of dioxin. Molecular and cellular biology 16, 2144-2150. Marlowe, J.L., and Puga, A. (2005). Aryl hydrocarbon receptor, cell cycle regulation, toxicity, and tumorigenesis. Journal of cellular biochemistry 96, 1174-1184. Massague, J. (2000). How cells read TGF-beta signals. Nature reviews Molecular cell biology 1, 169-178. Massague, J., and Chen, Y.G. (2000). Controlling TGF-beta signaling. Genes & development 14, 627-644. Massague, J., Seoane, J., and Wotton, D. (2005). Smad transcription factors. Genes & development 19, 2783-2810. Medici, D., Hay, E.D., and Olsen, B.R. (2008). Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Molecular biology of the cell 19, 4875-4887. Mendez, M.G., Kojima, S., and Goldman, R.D. (2010). Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24, 1838-1851. Meyer, B.K., and Perdew, G.H. (1999). Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization. Biochemistry 38, 8907-8917. Mimeault, M., and Batra, S.K. (2007). Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 18, 1605-1619. Moore, M., Ruh, M., Steinberg, M., and Safe, S. (1996). Isolation and characterization of variant benzo[a]pyrene-resistant T47D human breast-cancer cells. International journal of cancer Journal international du cancer 66, 117-123. Moore, M., Wang, X., Lu, Y.F., Wormke, M., Craig, A., Gerlach, J.H., Burghardt, R., Barhoumi, R., and Safe, S. (1994). Benzo[a]pyrene-resistant MCF-7 human breast cancer cells. A unique aryl hydrocarbon-nonresponsive clone. The Journal of biological chemistry 269, 11751-11759. Moustakas, A., and Heldin, C.H. (2005). Non-Smad TGF-beta signals. Journal of cell science 118, 3573-3584. Moustakas, A., and Heldin, C.H. (2012). Induction of epithelial-mesenchymal transition by transforming growth factor beta. Seminars in cancer biology 22, 446-454. Moustakas, A., Souchelnytskyi, S., and Heldin, C.H. (2001). Smad regulation in TGF-beta signal transduction. Journal of cell science 114, 4359-4369. Mulero-Navarro, S., Pozo-Guisado, E., Perez-Mancera, P.A., Alvarez-Barrientos, A., Catalina-Fernandez, I., Hernandez-Nieto, E., Saenz-Santamaria, J., Martinez, N., Rojas, J.M., Sanchez-Garcia, I., et al. (2005). Immortalized mouse mammary fibroblasts lacking dioxin receptor have impaired tumorigenicity in a subcutaneous mouse xenograft model. The Journal of biological chemistry 280, 28731-28741. Netherton, S.J., and Bonni, S. (2010). Suppression of TGFbeta-induced epithelial-mesenchymal transition like phenotype by a PIAS1 regulated sumoylation pathway in NMuMG epithelial cells. PloS one 5, e13971. Nieto, M.A. (2009). Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives. The International journal of developmental biology 53, 1541-1547. Opitz, C.A., Litzenburger, U.M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011). An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478, 197-203. Ozdamar, B., Bose, R., Barrios-Rodiles, M., Wang, H.R., Zhang, Y., and Wrana, J.L. (2005). Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 307, 1603-1609. Palermo, C.M., Westlake, C.A., and Gasiewicz, T.A. (2005). Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 44, 5041-5052. Peinado, H., Olmeda, D., and Cano, A. (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature reviews Cancer 7, 415-428. Peron, P., Rahmani, M., Zagar, Y., Durand-Schneider, A.M., Lardeux, B., and Bernuau, D. (2001). Potentiation of Smad transactivation by Jun proteins during a combined treatment with epidermal growth factor and transforming growth factor-beta in rat hepatocytes. role of phosphatidylinositol 3-kinase-induced AP-1 activation. The Journal of biological chemistry 276, 10524-10531. Peters, J.M., Narotsky, M.G., Elizondo, G., Fernandez-Salguero, P.M., Gonzalez, F.J., and Abbott, B.D. (1999). Amelioration of TCDD-induced teratogenesis in aryl hydrocarbon receptor (AhR)-null mice. Toxicological sciences : an official journal of the Society of Toxicology 47, 86-92. Poland, A., Clover, E., Kende, A.S., DeCamp, M., and Giandomenico, C.M. (1976). 3,4,3',4'-Tetrachloro azoxybenzene and azobenzene: potent inducers of aryl hydrocarbon hydroxylase. Science 194, 627-630. Portal-Nunez, S., Shankavaram, U.T., Rao, M., Datrice, N., Atay, S., Aparicio, M., Camphausen, K.A., Fernandez-Salguero, P.M., Chang, H., Lin, P., et al. (2012). Aryl hydrocarbon receptor-induced adrenomedullin mediates cigarette smoke carcinogenicity in humans and mice. Cancer research 72, 5790-5800. Puga, A., Marlowe, J., Barnes, S., Chang, C.Y., Maier, A., Tan, Z., Kerzee, J.K., Chang, X., Strobeck, M., and Knudsen, E.S. (2002). Role of the aryl hydrocarbon receptor in cell cycle regulation. Toxicology 181-182, 171-177. Ramos, K.S., Hadi Falahatpisheh, M., Nanez, A., and He, Q. (2006). Modulation of biological regulatory networks during nephrogenesis. Drug metabolism reviews 38, 677-683. Rico-Leo, E.M., Alvarez-Barrientos, A., and Fernandez-Salguero, P.M. (2013). Dioxin receptor expression inhibits basal and transforming growth factor beta-induced epithelial-to-mesenchymal transition. The Journal of biological chemistry 288, 7841-7856. Safe, S., Lee, S.O., and Jin, U.H. (2013). Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicological sciences : an official journal of the Society of Toxicology 135, 1-16. Santiago-Josefat, B., Mulero-Navarro, S., Dallas, S.L., and Fernandez-Salguero, P.M. (2004). Overexpression of latent transforming growth factor-beta binding protein 1 (LTBP-1) in dioxin receptor-null mouse embryo fibroblasts. Journal of cell science 117, 849-859. Seifert, A., Rau, S., Kullertz, G., Fischer, B., and Santos, A.N. (2009). TCDD induces cell migration via NFATc1/ATX-signaling in MCF-7 cells. Toxicology letters 184, 26-32. Shimba, S., Komiyama, K., Moro, I., and Tezuka, M. (2002). Overexpression of the aryl hydrocarbon receptor (AhR) accelerates the cell proliferation of A549 cells. Journal of biochemistry 132, 795-802. Siegel, P.M., Shu, W., and Massague, J. (2003). Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-beta-mediated epithelial cell growth suppression. The Journal of biological chemistry 278, 35444-35450. Sinal, C.J., and Bend, J.R. (1997). Aryl hydrocarbon receptor-dependent induction of cyp1a1 by bilirubin in mouse hepatoma hepa 1c1c7 cells. Molecular pharmacology 52, 590-599. Subramanyam, D., Lamouille, S., Judson, R.L., Liu, J.Y., Bucay, N., Derynck, R., and Blelloch, R. (2011). Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nature biotechnology 29, 443-448. Temchura, V.V., Frericks, M., Nacken, W., and Esser, C. (2005). Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo. European journal of immunology 35, 2738-2747. Thiery, J.P., Acloque, H., Huang, R.Y., and Nieto, M.A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890. Thiery, J.P., and Sleeman, J.P. (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nature reviews Molecular cell biology 7, 131-142. Tran, C., Richmond, O., Aaron, L., and Powell, J.B. (2013). Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen independent signaling and growth in (C4-2) prostate cancer cells. Biochemical pharmacology 85, 753-762. Tripathi, M.K., Misra, S., Khedkar, S.V., Hamilton, N., Irvin-Wilson, C., Sharan, C., Sealy, L., and Chaudhuri, G. (2005). Regulation of BRCA2 gene expression by the SLUG repressor protein in human breast cells. The Journal of biological chemistry 280, 17163-17171. Vinas-Castells, R., Beltran, M., Valls, G., Gomez, I., Garcia, J.M., Montserrat-Sentis, B., Baulida, J., Bonilla, F., de Herreros, A.G., and Diaz, V.M. (2010). The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation. The Journal of biological chemistry 285, 3794-3805. Wan, M., Cao, X., Wu, Y., Bai, S., Wu, L., Shi, X., Wang, N., and Cao, X. (2002). Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. EMBO reports 3, 171-176. Wang, C.K., Chang, H., Chen, P.H., Chang, J.T., Kuo, Y.C., Ko, J.L., and Lin, P. (2009). Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas. International journal of cancer Journal international du cancer 125, 807-815. Wang, F.E., Zhang, C., Maminishkis, A., Dong, L., Zhi, C., Li, R., Zhao, J., Majerciak, V., Gaur, A.B., Chen, S., et al. (2010a). MicroRNA-204/211 alters epithelial physiology. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24, 1552-1571. Wang, Y., Fan, Y., and Puga, A. (2010b). Dioxin exposure disrupts the differentiation of mouse embryonic stem cells into cardiomyocytes. Toxicological sciences : an official journal of the Society of Toxicology 115, 225-237. Wicki, A., Lehembre, F., Wick, N., Hantusch, B., Kerjaschki, D., and Christofori, G. (2006). Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer cell 9, 261-272. Wolff, S., Harper, P.A., Wong, J.M., Mostert, V., Wang, Y., and Abel, J. (2001). Cell-specific regulation of human aryl hydrocarbon receptor expression by transforming growth factor-beta(1). Molecular pharmacology 59, 716-724. Xu, J., and Attisano, L. (2000). Mutations in the tumor suppressors Smad2 and Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America 97, 4820-4825. Xu, J., Lamouille, S., and Derynck, R. (2009). TGF-beta-induced epithelial to mesenchymal transition. Cell research 19, 156-172. Yagel, S., Feinmesser, R., Waghorne, C., Lala, P.K., Breitman, M.L., and Dennis, J.W. (1989). Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes. International journal of cancer Journal international du cancer 44, 685-690. Yan, X., Liu, Z., and Chen, Y. (2009). Regulation of TGF-beta signaling by Smad7. Acta biochimica et biophysica Sinica 41, 263-272. Yilmaz, M., and Christofori, G. (2009). EMT, the cytoskeleton, and cancer cell invasion. Cancer metastasis reviews 28, 15-33. Yoshino, I., Kometani, T., Shoji, F., Osoegawa, A., Ohba, T., Kouso, H., Takenaka, T., Yohena, T., and Maehara, Y. (2007). Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in lung cancer cells. Cancer 110, 369-374. Zhang, S., Lei, P., Liu, X., Li, X., Walker, K., Kotha, L., Rowlands, C., and Safe, S. (2009). The aryl hydrocarbon receptor as a target for estrogen receptor-negative breast cancer chemotherapy. Endocrine-related cancer 16, 835-844. Zhang, Y., Chang, C., Gehling, D.J., Hemmati-Brivanlou, A., and Derynck, R. (2001). Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 98, 974-979. Zhou, Q., Fan, J., Ding, X., Peng, W., Yu, X., Chen, Y., and Nie, J. (2010). TGF-{beta}-induced MiR-491-5p expression promotes Par-3 degradation in rat proximal tubular epithelial cells. The Journal of biological chemistry 285, 40019-40027. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5188 | - |
| dc.description.abstract | 多環芳香烴受體 (Aryl Hydrocarbon Receptor, AhR)為細胞當中一配體活化之轉錄因子，當細胞接觸到多環芳香烴 (Polycyclic Aromatic Hydrocarbon, PAHs)時，PAHs會與AhR結合並使其受到活化而進入細胞核中，進而啟動目標基因生合成Cytochrome P450 (CYP1A1、CYP1B1)，並將外來物質氧化還原以利進行酵素代謝反應。上皮細胞間質轉換 (Epithelial- Mesenchymal Transition, EMT)是指細胞從上皮細胞型態轉變為間質細胞型態的一種過程，而在癌細胞當中則被認為與腫瘤轉移 (Metastasis)能力有關。過去研究顯示，PAHs會透過活化AhR，引起癌細胞發生EMT的現象，目前僅有少數文獻探討未活化的AhR是否與EMT有相關，機制仍舊尚未明朗，因此本篇研究目的旨在探討，不存在配體的情形之下，透過in vitro Transfection方式於肺癌細胞株中大量表現AhR，觀察是否影響EMT現象以及細胞轉移能力改變並探討其調控機制。實驗結果顯示，在大量表現AhR後，細胞中的Epithelial marker增加且Mesenchymal markers表現量會減少，顯示細胞EMT現象可能受到抑制，並且可能原因為EMT相關轉錄因子snail/slug、ID1表現減少，進一步探討其調節機制發現，細胞內的Smad4蛋白表現量發生改變，而Smad4是參與TGF-β訊號傳遞中重要的伴隨蛋白，能夠幫助受活化的調節型smad共同進核，且過去研究指出TGF-β能夠誘使細胞進行EMT，故一旦受到抑制，會造成細胞呈現MET發展，此時細胞的轉移能力也會受到抑制，過去研究發現，Smad4的蛋白表現受Jun活化結合蛋白 (Jun-Activation Domain-Binding Protein, Jab1)的影響，Jab1為一種E3-ubiquitin lagase，會使Smad4 ubiquitination後送至26s proteasome 進行降解，而本實驗結果也證實，AhR會造成Jab1與Smad4間的蛋白結合能力增強，進而導致Smad4受到降解的程度強化，最終造成TGF-β訊號傳遞減弱。最後，在體外的細胞轉移試驗 (Migration assay)中也可以發現細胞的遷移以及侵襲 (Invasion)能力明顯降低，顯示AhR的大量表現確實能夠抑制癌細胞轉移能力。並且利用shAhR進行靜默 (silence)作為反證，細胞有促進EMT的現象。綜合以上實驗結果得知，在肺癌細胞株中，未活化的AhR能夠透過Jab1調控smad4的蛋白表現量，達到抑制TGF-β的訊號傳遞，降低EMT相關轉錄因子的生合成，進而導致癌細胞無法進行EMT，而使得癌細胞的遷移能力受到干擾。 | zh_TW |
| dc.description.abstract | Backgrounds: The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that forms a complex with its ligand such as TCDD to activate target genes Epithelial to mesenchymal transition (EMT) is a process that epithelial cells are converted to invasive mesenchymal cells, and this process involved tumor metastasis from original cancer to distal. The role of ligand-independent AhR function in cell EMT was investigated in this study. Results: Epithelial markers were induced and mesenchymal markers were inhibited in AhR-overexpressed cell. At the same time, the expression of EMT-related transcriptional factors Snail/slug were also decreased. Interestingly, Smad4 degradation was enhanced in AhR-overexpressed lung cancer cells. Smad4 itself is a co-translocational factor from cytoplasma to nuclear when regulated-smad phosphorylate by TGF-β. TGF-β plays as a potent factor of cancer progression through the induction of EMT. If TGF-β pathway has be inhibited by suppression of smad4, the cancer cell migration will decrease via mesenchymal to epithelial transition (MET). Preliminary studies have shown that Jab1 interacts directly with smad4 and induces its ubiquitination for degradation via 26s proteasome. Our data show that AhR able to increase interaction between Jab1 and smad4, which might increase degradation of smad4 though 26s proteasome pathway. In addition, Cell migration and cell invasion ability were decreased in AhR overexpressed cells. Conclusion: Our data suggest that AhR affects TGF-β function through Jab1-induced Smad4 degradation by proteasome and resulted in tumor metastasis suppression via EMT reduction in lung cancer cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-15T17:53:13Z (GMT). No. of bitstreams: 1 ntu-103-R00447012-1.pdf: 3433484 bytes, checksum: 1b9134ba4d7e1abc84501ae2f0c689aa (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 口試委員審定書 i
致謝 ii 中文摘要 iii 英文摘要 v 縮寫表 vi 第一章 緒論 (Introduction) 3 1.1多環芳香烴受體 (Aryl Hydrocarbon Receptor, AhR) 4 1.2 上皮間質轉換 (Epithelial- mesenchymal transition, EMT) 7 1.3 轉型生長因子β (Transforming growth factor β, TGF-β) 9 1.4 TGF-β與EMT 13 1.5 AhR與EMT 15 1.6研究動機 17 第二章 材料與方法 (Materials and Methods) 18 2.1實驗材料 19 2.1.1細胞株 (Cell line) 19 2.1.2抗體 (Antibody) 19 2.1.3質體 (Plasmid) 19 2.1.4 實驗藥品與試劑 (Drug and Reagent) 20 2.2實驗方法 21 2.2.1肺癌細胞培養與繼代 (Cell culture and Subculture) 21 2.2.2細胞總蛋白液收集 (Cell lysate collection) 22 2.2.3西方墨點法 (Western blot) 23 2.2.4質體轉染 (Plasmid transfection) 23 2.2.5慢病毒製備與感染 (Lentivirus production and infection) 24 2.2.6反轉錄聚合酶連鎖反應 (Reverse Transcription Polymerase Chain Reaction, RT-PCR) 24 2.2.7免疫沉澱法 (Immunoprecipitation) 26 2.2.8細胞侵襲與傷口癒合法 (Cell invasion and wound healing) 26 2.2.9 SBE冷光報導基因分析 (SBE Luciferase reporter assay) 26 2.2.10 統計分析 (statistic analysis) 27 第三章 結果 (Results) 28 3.1 於肺癌細胞中大量表現AhR能夠透過EMT抑制細胞侵襲能力 29 3.2 AhR蛋白透過抑制smad4表現進而干擾TGF-β/BMP pathway的活化 30 3.3 AhR的蛋白表現量增加會促進smad4透過泛素-蛋白酶體路徑的降解 31 3.4 大量表現AhR導致Jab1以及smad4間的交互作用力增強 32 3.5 AhR抑制TGF-β/BMP pathway的目標蛋白 33 3.6 AhR參與肺癌細胞透過EMT現象所導致的侵襲能力改變 34 第四章 討論 (Discussion) 35 第五章 結論 (Conclusion) 44 參考文獻 (References) 46 圖表 (Figures and Tables) 67 Figure 1. The Role of Aryl hydrocarbon receptor (AhR) in EMT of Lung Cancer In Vitro 71 Figure 2. AhR inhibits Smad4 and Represses the Activity of TGF-β Pathway. 73 Figure 3. Up-regulated AhR induces Smad4 Degradation via ubiquitin proteasome Pathway. 75 Figure 4. Overexpression of AhR induces interaction between Jab1 and Smad4. 76 Figure 5. AhR protein suppresses EMT-related target gene of TGF-β Pathway. 78 Figure 6. AhR protein involves lung cancer cells migratiove ability change. 80 Figure 7 The signaling pathway of AhR inhibit cell migration. 81 Table 1 82 | |
| dc.language.iso | zh-TW | |
| dc.subject | Jab1 | zh_TW |
| dc.subject | 多環芳香烴受體 | zh_TW |
| dc.subject | TGF-β | zh_TW |
| dc.subject | 上皮間質轉換 | zh_TW |
| dc.subject | Smad4 | zh_TW |
| dc.subject | TGF-β | en |
| dc.subject | Jab1 | en |
| dc.subject | Smad4 | en |
| dc.subject | Epithelial to mesenchymal transiton | en |
| dc.subject | Aryl hydrocarbon receptor | en |
| dc.title | 多環芳香烴受體於人類肺癌細胞株中透過Smad4降解引發TGF-β訊號傳遞路徑抑制之機制探討 | zh_TW |
| dc.title | Aryl Hydrocarbon Receptor Inhibits TGF-β Pathway through Smad4 Degradation in Human Lung Carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭幼文(Yu-Wen Cheng),李珍珍(Chen-Chen Lee) | |
| dc.subject.keyword | 多環芳香烴受體,TGF-β,上皮間質轉換,Smad4,Jab1, | zh_TW |
| dc.subject.keyword | Aryl hydrocarbon receptor,TGF-β,Epithelial to mesenchymal transiton,Smad4,Jab1, | en |
| dc.relation.page | 82 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2014-12-01 | |
| 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-103-1.pdf | 3.35 MB | Adobe PDF | 檢視/開啟 |
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。