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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊性芳(Hsin-Fang Yang-Yen) | |
dc.contributor.author | Shih-Yen Weng | en |
dc.contributor.author | 翁仕彥 | zh_TW |
dc.date.accessioned | 2021-06-15T05:01:58Z | - |
dc.date.available | 2011-02-01 | |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-28 | |
dc.identifier.citation | 1. Aguilar F, Harris CC, Sun T, Hollstein M, Cerutti P. Geographic variation of p53 mutational profile in nonmalignant human liver. Science 1994 May 27;264(5163):1317-1319.
2. Armstrong JF, Kaufman MH, Harrison DJ, Clarke AR. High-frequency developmental abnormalities in p53-deficient mice. Curr Biol 1995 Aug 1;5(8):931-936. 3. Badvie S. Hepatocellular carcinoma. Postgrad Med J 2000 Jan;76(891):4-11. 4. Bellamy CO, Clarke AR, Wyllie AH, Harrison DJ. p53 Deficiency in liver reduces local control of survival and proliferation, but does not affect apoptosis after DNA damage. FASEB J 1997 Jun;11(7):591-599. 5. Betz UA, Bloch W, van den Broek M, Yoshida K, Taga T, Kishimoto T, et al. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med 1998 Nov 16;188(10):1955-1965. 6. Calogero S, Grassi F, Aguzzi A, Voigtlander T, Ferrier P, Ferrari S, et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet 1999 Jul;22(3):276-280. 7. Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 2006 May;9(5):351-365. 8. Chen GG, Merchant JL, Lai PB, Ho RL, Hu X, Okada M, et al. Mutation of p53 in recurrent hepatocellular carcinoma and its association with the expression of ZBP-89. Am J Pathol 2003 Jun;162(6):1823-1829. 9. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 2005 Feb 4;17(3):393-403. 10. Chipuk JE, Bouchier-Hayes L, Kuwana T, Newmeyer DD, Green DR. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 2005 Sep 9;309(5741):1732-1735. 11. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 2004 Feb 13;303(5660):1010-1014. 12. Chipuk JE, Maurer U, Green DR, Schuler M. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 2003 Nov;4(5):371-381. 13. Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 1993 Apr 29;362(6423):849-852. 14. Clotman F, Lannoy VJ, Reber M, Cereghini S, Cassiman D, Jacquemin P, et al. The onecut transcription factor HNF6 is required for normal development of the biliary tract. Development 2002 Apr;129(8):1819-1828. 15. Cornell RP, Liljequist BL, Bartizal KF. Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice. Hepatology 1990 Jun;11(6):916-922. 16. Court FG, Wemyss-Holden SA, Dennison AR, Maddern GJ. The mystery of liver regeneration. Br J Surg 2002 Sep;89(9):1089-1095. 17. Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 1996 Nov 22;274(5291):1379-1383. 18. Dal Bello B, Rosa L, Campanini N, Tinelli C, Torello Viera F, D'Ambrosio G, et al. Glutamine synthetase immunostaining correlates with pathologic features of hepatocellular carcinoma and better survival after radiofrequency thermal ablation. Clin Cancer Res Apr 1;16(7):2157-2166. 19. Deng X, Gao F, Flagg T, Anderson J, May WS. Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol 2006 Jun;26(12):4421-4434. 20. Derenne S, Monia B, Dean NM, Taylor JK, Rapp MJ, Harousseau JL, et al. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood 2002 Jul 1;100(1):194-199. 21. Ding Q, He X, Hsu JM, Xia W, Chen CT, Li LY, et al. Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol 2007 Jun;27(11):4006-4017. 22. Donehower LA. The p53-deficient mouse: a model for basic and applied cancer studies. Semin Cancer Biol 1996 Oct;7(5):269-278. 23. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Jr., Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992 Mar 19;356(6366):215-221. 24. Douarin NM. An experimental analysis of liver development. Med Biol 1975 Dec;53(6):427-455. 25. Dumble ML, Knight B, Quail EA, Yeoh GC. Hepatoblast-like cells populate the adult p53 knockout mouse liver: evidence for a hyperproliferative maturation-arrested stem cell compartment. Cell Growth Differ 2001 May;12(5):223-231. 26. Dzhagalov I, Dunkle A, He YW. The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages. J Immunol 2008 Jul 1;181(1):521-528. 27. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006 Sep;6(9):674-687. 28. Feitelson MA, Sun B, Satiroglu Tufan NL, Liu J, Pan J, Lian Z. Genetic mechanisms of hepatocarcinogenesis. Oncogene 2002 Apr 11;21(16):2593-2604. 29. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003 Aug;125(2):437-443. 30. Fleischer B, Schulze-Bergkamen H, Schuchmann M, Weber A, Biesterfeld S, Muller M, et al. Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma. Int J Oncol 2006 Jan;28(1):25-32. 31. Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, et al. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med 1995 Nov 1;182(5):1223-1230. 32. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992 Nov;119(3):493-501. 33. Gillet R, Grimber G, Bennoun M, Caron de Fromentel C, Briand P, Joulin V. The consequence of p53 overexpression for liver tumor development and the response of transformed murine hepatocytes to genotoxic agents. Oncogene 2000 Jul 20;19(31):3498-3507. 34. Gollin SM. Mechanisms leading to chromosomal instability. Semin Cancer Biol 2005 Feb;15(1):33-42. 35. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998 Aug 28;281(5381):1309-1312. 36. Gregorieff A, Clevers H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev 2005 Apr 15;19(8):877-890. 37. Guicciardi ME, Gores GJ. Apoptosis: a mechanism of acute and chronic liver injury. Gut 2005 Jul;54(7):1024-1033. 38. Hacker G. The morphology of apoptosis. Cell Tissue Res 2000 Jul;301(1):5-17. 39. Harvey M, McArthur MJ, Montgomery CA, Jr., Bradley A, Donehower LA. Genetic background alters the spectrum of tumors that develop in p53-deficient mice. FASEB J 1993 Jul;7(10):938-943. 40. Hengartner MO. The biochemistry of apoptosis. Nature 2000 Oct 12;407(6805):770-776. 41. Hentsch B, Lyons I, Li R, Hartley L, Lints TJ, Adams JM, et al. Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut. Genes Dev 1996 Jan 1;10(1):70-79. 42. Hikita H, Takehara T, Shimizu S, Kodama T, Li W, Miyagi T, et al. Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver. Hepatology 2009 Oct;50(4):1217-1226. 43. Hsiao YC, Chang HH, Tsai CY, Jong YJ, Horng LS, Lin SF, et al. Coat color-tagged green mouse with EGFP expressed from the RNA polymerase II promoter. Genesis 2004 Jun;39(2):122-129. 44. Huh CG, Factor VM, Sanchez A, Uchida K, Conner EA, Thorgeirsson SS. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A 2004 Mar 30;101(13):4477-4482. 45. Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K, et al. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer 2001 May 18;84(10):1377-1383. 46. Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol 1994 Jan 1;4(1):1-7. 47. Jaeschke H, Gujral JS, Bajt ML. Apoptosis and necrosis in liver disease. Liver Int 2004 Apr;24(2):85-89. 48. Jiang P, Du W, Heese K, Wu M. The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis. Mol Cell Biol 2006 Dec;26(23):9071-9082. 49. Jung J, Zheng M, Goldfarb M, Zaret KS. Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science 1999 Jun 18;284(5422):1998-2003. 50. Keng VW, Yagi H, Ikawa M, Nagano T, Myint Z, Yamada K, et al. Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage. Biochem Biophys Res Commun 2000 Oct 5;276(3):1155-1161. 51. Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991 May 23;351(6324):317-320. 52. Kitada T, Seki S, Kawakita N, Kuroki T, Monna T. Telomere shortening in chronic liver diseases. Biochem Biophys Res Commun 1995 Jun 6;211(1):33-39. 53. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 2000 Dec;7(12):1166-1173. 54. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3516-3520. 55. Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, et al. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol 1996 May;148(5):1567-1576. 56. Krajewski S, Bodrug S, Krajewska M, Shabaik A, Gascoyne R, Berean K, et al. Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. Am J Pathol 1995 Jun;146(6):1309-1319. 57. Kreamer BL, Staecker JL, Sawada N, Sattler GL, Hsia MT, Pitot HC. Use of a low-speed, iso-density percoll centrifugation method to increase the viability of isolated rat hepatocyte preparations. In Vitro Cell Dev Biol 1986 Apr;22(4):201-211. 58. Kruse JP, Gu W. Modes of p53 regulation. Cell 2009 May 15;137(4):609-622. 59. Kuo CJ, Conley PB, Chen L, Sladek FM, Darnell JE, Jr., Crabtree GR. A transcriptional hierarchy involved in mammalian cell-type specification. Nature 1992 Jan 30;355(6359):457-461. 60. Kuperwasser C, Hurlbut GD, Kittrell FS, Dickinson ES, Laucirica R, Medina D, et al. Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome. Am J Pathol 2000 Dec;157(6):2151-2159. 61. Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, et al. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A 1996 Jun 11;93(12):5860-5865. 62. Lazzerini Denchi E, Celli G, de Lange T. Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplication. Genes Dev 2006 Oct 1;20(19):2648-2653. 63. Leu JI, Dumont P, Hafey M, Murphy ME, George DL. Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol 2004 May;6(5):443-450. 64. Liu H, Peng HW, Cheng YS, Yuan HS, Yang-Yen HF. Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Mol Cell Biol 2005 Apr;25(8):3117-3126. 65. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 1993 Apr 29;362(6423):847-849. 66. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008 Mar 13;27(12):1749-1758. 67. Macdonald A, Crowder K, Street A, McCormick C, Saksela K, Harris M. The hepatitis C virus non-structural NS5A protein inhibits activating protein-1 function by perturbing ras-ERK pathway signaling. J Biol Chem 2003 May 16;278(20):17775-17784. 68. Majumder M, Ghosh AK, Steele R, Ray R, Ray RB. Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. J Virol 2001 Feb;75(3):1401-1407. 69. Malhi H, Gores GJ, Lemasters JJ. Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology 2006 Feb;43(2 Suppl 1):S31-44. 70. Marrogi AJ, Khan MA, van Gijssel HE, Welsh JA, Rahim H, Demetris AJ, et al. Oxidative stress and p53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma. J Natl Cancer Inst 2001 Nov 7;93(21):1652-1655. 71. Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 2006 Mar 17;21(6):749-760. 72. McClain CJ, Hill DB, Song Z, Deaciuc I, Barve S. Monocyte activation in alcoholic liver disease. Alcohol 2002 May;27(1):53-61. 73. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997 Apr 4;276(5309):60-66. 74. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 2003 Mar;11(3):577-590. 75. Miura N, Horikawa I, Nishimoto A, Ohmura H, Ito H, Hirohashi S, et al. Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis. Cancer Genet Cytogenet 1997 Jan;93(1):56-62. 76. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995 Jan 27;80(2):293-299. 77. Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 2007 Sep 13;26(42):6133-6140. 78. Murakami Y, Saigo K, Takashima H, Minami M, Okanoue T, Brechot C, et al. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut 2005 Aug;54(8):1162-1168. 79. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 2001 Mar;7(3):683-694. 80. Natori S, Rust C, Stadheim LM, Srinivasan A, Burgart LJ, Gores GJ. Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis. J Hepatol 2001 Feb;34(2):248-253. 81. Nijhara R, Jana SS, Goswami SK, Rana A, Majumdar SS, Kumar V, et al. Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. J Virol 2001 Nov;75(21):10348-10358. 82. Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, et al. Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev 2003 Jun 15;17(12):1475-1486. 83. Ockner RK. Apoptosis and liver diseases: recent concepts of mechanism and significance. J Gastroenterol Hepatol 2001 Mar;16(3):248-260. 84. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, et al. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 2000 May 12;288(5468):1053-1058. 85. Opferman JT, Iwasaki H, Ong CC, Suh H, Mizuno S, Akashi K, et al. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005 Feb 18;307(5712):1101-1104. 86. Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 2003 Dec 11;426(6967):671-676. 87. Park JY, Park WS, Nam SW, Kim SY, Lee SH, Yoo NJ, et al. Mutations of beta-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis. Liver Int 2005 Feb;25(1):70-76. 88. Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003 Jan;10(1):26-35. 89. Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, et al. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem 1999 Jan 1;274(1):305-315. 90. Purdie CA, Harrison DJ, Peter A, Dobbie L, White S, Howie SE, et al. Tumour incidence, spectrum and ploidy in mice with a large deletion in the p53 gene. Oncogene 1994 Feb;9(2):603-609. 91. Puthier D, Bataille R, Amiot M. IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway. Eur J Immunol 1999 Dec;29(12):3945-3950. 92. Reed JC. Double identity for proteins of the Bcl-2 family. Nature 1997 Jun 19;387(6635):773-776. 93. Reimold AM, Etkin A, Clauss I, Perkins A, Friend DS, Zhang J, et al. An essential role in liver development for transcription factor XBP-1. Genes Dev 2000 Jan 15;14(2):152-157. 94. Riedl SJ, Salvesen GS. The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 2007 May;8(5):405-413. 95. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008 May;9(5):402-412. 96. Rinkenberger JL, Horning S, Klocke B, Roth K, Korsmeyer SJ. Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev 2000 Jan 1;14(1):23-27. 97. Rossi JM, Dunn NR, Hogan BL, Zaret KS. Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev 2001 Aug 1;15(15):1998-2009. 98. Sah VP, Attardi LD, Mulligan GJ, Williams BO, Bronson RT, Jacks T. A subset of p53-deficient embryos exhibit exencephaly. Nat Genet 1995 Jun;10(2):175-180. 99. Sakamoto T, Liu Z, Murase N, Ezure T, Yokomuro S, Poli V, et al. Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology 1999 Feb;29(2):403-411. 100. Schulze-Bergkamen H, Fleischer B, Schuchmann M, Weber A, Weinmann A, Krammer PH, et al. Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. BMC Cancer 2006;6:232. 101. Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol 1976;13:29-83. 102. Seoane J, Le HV, Massague J. Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature 2002 Oct 17;419(6908):729-734. 103. Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005;25(2):143-154. 104. Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999 Jun 3;399(6735):483-487. 105. Sieghart W, Losert D, Strommer S, Cejka D, Schmid K, Rasoul-Rockenschaub S, et al. Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy. J Hepatol 2006 Jan;44(1):151-157. 106. Sosa-Pineda B, Wigle JT, Oliver G. Hepatocyte migration during liver development requires Prox1. Nat Genet 2000 Jul;25(3):254-255. 107. Speidel D. Transcription-independent p53 apoptosis: an alternative route to death. Trends Cell Biol Jan;20(1):14-24. 108. Speidel D, Helmbold H, Deppert W. Dissection of transcriptional and non-transcriptional p53 activities in the response to genotoxic stress. Oncogene 2006 Feb 9;25(6):940-953. 109. Tarn C, Lee S, Hu Y, Ashendel C, Andrisani OM. Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes. J Biol Chem 2001 Sep 14;276(37):34671-34680. 110. Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2004 Oct;5(10):836-847. 111. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008 Mar;9(3):231-241. 112. Thallinger C, Wolschek MF, Wacheck V, Maierhofer H, Gunsberg P, Polterauer P, et al. Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model. J Invest Dermatol 2003 Jun;120(6):1081-1086. 113. Tian H, Wittmack EK, Jorgensen TJ. p21WAF1/CIP1 antisense therapy radiosensitizes human colon cancer by converting growth arrest to apoptosis. Cancer Res 2000 Feb 1;60(3):679-684. 114. Tian JM, Schibler U. Tissue-specific expression of the gene encoding hepatocyte nuclear factor 1 may involve hepatocyte nuclear factor 4. Genes Dev 1991 Dec;5(12A):2225-2234. 115. Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006 Dec;6(12):909-923. 116. Tsukada T, Tomooka Y, Takai S, Ueda Y, Nishikawa S, Yagi T, et al. Enhanced proliferative potential in culture of cells from p53-deficient mice. Oncogene 1993 Dec;8(12):3313-3322. 117. Urabe Y, Nouso K, Higashi T, Nakatsukasa H, Hino N, Ashida K, et al. Telomere length in human liver diseases. Liver 1996 Oct;16(5):293-297. 118. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 2006 Nov;10(5):389-399. 119. Vick B, Weber A, Urbanik T, Maass T, Teufel A, Krammer PH, et al. Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes. Hepatology 2009 Feb;49(2):627-636. 120. Vilborg A, Glahder JA, Wilhelm MT, Bersani C, Corcoran M, Mahmoudi S, et al. The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element. Proc Natl Acad Sci U S A 2009 Sep 15;106(37):15756-15761. 121. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007 Apr;8(4):275-283. 122. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer 2002 Aug;2(8):594-604. 123. Wang JM, Chao JR, Chen W, Kuo ML, Yen JJ, Yang-Yen HF. The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB. Mol Cell Biol 1999 Sep;19(9):6195-6206. 124. Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, et al. Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice. Hepatology 2010 Apr;51(4):1226-1236. 125. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001 Apr 27;292(5517):727-730. 126. Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 2005 Jun 1;19(11):1294-1305. 127. Yamada Y, Kirillova I, Peschon JJ, Fausto N. Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci U S A 1997 Feb 18;94(4):1441-1446. 128. Yang CY, Lin NH, Lee JM, Huang CY, Min HJ, Yen JJ, et al. Promoter knock-in mutations reveal a role of Mcl-1 in thymocyte-positive selection and tissue or cell lineage-specific regulation of Mcl-1 expression. J Immunol 2009 Mar 1;182(5):2959-2968. 129. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 2001 Mar;7(3):673-682. 130. Zaret KS. Regulatory phases of early liver development: paradigms of organogenesis. Nat Rev Genet 2002 Jul;3(7):499-512. 131. Zhong Q, Gao W, Du F, Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 2005 Jul 1;121(7):1085-1095. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46291 | - |
dc.description.abstract | Mcl-1缺失的肝臟細胞有細胞凋亡的傾向。而腫瘤抑制因子p53則於細胞凋亡控制以及其他細胞的反應上扮演重要的角色。本研究目的在於檢視在Mcl-1缺失導致的細胞凋亡,p53是否參與其中。本研究利用專一性剔除肝臟Mcl-1的小鼠(Alb-Mcl-1-/-),並比較其於p53存在與否之下的特性。
Alb-Mcl-1-/-小鼠雖可正常存活,其肝臟細胞卻傾向細胞凋亡,且發現p53稍微上升的現象。為了檢視p53在其間的功能,Alb-Mcl-1-/-及p53-/- 雙重突變 (DKO)的小鼠因此被分析及檢視。出乎意料的是,雖然p53缺失的小鼠發育是正常的,大約60%的DKO小鼠卻在新生的期間相繼死亡。進一步分析更顯示這樣的死亡可能與肝臟細胞分化的減損進而導致機能喪失有關。此外,相較於Alb-Mcl-1-/-小鼠,存活至成鼠的DKO小鼠顯現更為嚴重的肝臟損傷,顯示p53在Alb-Mcl-1-/-小鼠的肝臟中活化並促進細胞存活。在微陣列及定量PCR的實驗結果中顯示p53下游中一個促進存活的分子p21,有可能在其間參與p53保護Alb-Mcl-1-/-小鼠肝臟的角色。最後,我們也發現p53的缺失,加劇了Alb-Mcl-1-/-小鼠的肝臟纖維化及肝癌的進程。 綜合以上,本研究發現在保護免於肝臟損傷、纖維化及肝癌上,Mcl-1及p53之間存在著非預期的協同效應。 | zh_TW |
dc.description.abstract | Mcl-1-deficient hepatocytes are prone to undergo apoptosis. The tumor suppressor protein p53 plays an important role in apoptosis control as well as other cellular responses. To test whether p53 was involved in Mcl-1 deficiency-induced apoptosis of hepatocytes, hepatocyte-specific Mcl-1 knockout (Alb-Mcl-1-/-) mice and Alb-Mcl-1-/- mice in wild-type or p53-deficient background were generated and characterized. The results showed that Alb-Mcl-1-/- mice were viable, but their liver cells were prone to undergo apoptosis and manifested a slightly elevated level of p53. To examine the role of p53 in Alb-Mcl-1-/- livers, Alb-Mcl-1-/- mice without p53 (DKO mice) were characterized. Unexpectedly, although p53-deficient mice appeared to be developmentally normal, DKO mice were highly susceptible to neonatal death (~60%). Further analysis revealed that such early lethality was likely due to hepatic failure caused by a marked reduction of fully-differentiated hepatocytes at the perinatal/neonatal stage. Moreover, those DKO mice that did survive to adulthood manifested more severe liver damage than Alb-Mcl-1-/- mice, suggesting that p53 was activated in Alb-Mcl-1-/- livers to promote cell survival. Microarray followed by quantitative PCR analysis suggests that p21Waf1/Cip1, one p53 target gene with apoptosis-inhibitory function, is likely involved in the protective role of p53 in Alb-Mcl-1-/- livers. Last, we demonstrated that loss of p53 exacerbated liver fibrosis and tumor development in Alb-Mcl-1-/- mice. In summary, this study revealed an unexpected synergism between Mcl-1 and p53 in protecting from hepatic injury, fibrosis and cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:01:58Z (GMT). No. of bitstreams: 1 ntu-99-D90448006-1.pdf: 2817140 bytes, checksum: 0c7429b13f892535b7b6773855dea754 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 中文摘要……………………………………………………..VIII
Abstract……………………………………………………….IX Introduction…………………………………………………...1 Material and methods………………………………………..18 Mice……………………………………………………………..18 Generation of a conditional allele of the Mcl-1 gene………………………..18 Genotyping………………………………………………………..19 Determination of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and total bilirubin levels…………………………..……..20 Histological analysis and immunofluorescence microscopy…………………..20 Oil Red O staining…………………………………………………..21 Immunohistochemistry……………………………………………….21 In vivo BrdU labeling………………………………………………..22 Partial hepatectomy…………………………………………………22 Isolation of hepatocytes and determination of DNA contents…………………23 Determination of serum interleukin-6 (IL-6) and tumor necrosis factor (TNF-α)levels……………………23 Western blotting Analysis……………………24 TUNEL staining…………………………………………………..25 Real-Time quantitative PCR…………………………………………25 Statistical analysis…………………………………………………26 Results………………………………………………………..27 Loss of Mcl-1 results in enhanced apoptosis and proliferation of hepatocytes…...27 Transgenic over-expression of human MCL-1 rescued the liver phenotype of Alb-Mcl-1-/- mice………………………………………………….27 Combined loss of Mcl-1 and p53 in liver increases the susceptibility of mice to early postnatal death……………………………………………………28 p53 is activated in Alb-Mcl-1-/- livers to promote hepatocyte survival…………31 A limited subset of p53 target genes is activated in Alb-Mcl-1-/- but not DKO livers……………………………………………………………31 p53 deficiency accelerates the onset of fibrosis and fat accumulation in Alb-Mcl-1-/- livers………………………………………………….33 Loss of p53 tends to promote liver tumor development in Alb-Mcl-1-/- mice……34 Increased sensitivity of DKO mice to CD95-mediated apoptosis…………….35 Discussion…………………………………………………....37 Figures and legends…………………………………….........42 Tables………………………………………………………....71 References……………………………………………………74 Appendix | |
dc.language.iso | en | |
dc.title | p53與Mcl-1蛋白於保護肝臟免於損傷、纖維化及癌症之協同效應研究 | zh_TW |
dc.title | Synergism between p53 and Mcl-1 in protecting from hepatic injury, fibrosis and cancer | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李芳仁(Fang-Jen Lee),嚴仲陽(Jeffrey Jong-Young Yen),蔡亭芬(Ting-Fen Tsai),陳俊銘(Chun-Ming Chen) | |
dc.subject.keyword | 肝臟,Mcl-1,p53,細胞凋亡,腫瘤, | zh_TW |
dc.subject.keyword | Liver,Mcl-1,p53,apoptosis,tumor, | en |
dc.relation.page | 85 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-07-28 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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