Accelerating cancer modeling with RNAi and nongermline genetically engineered mouse models

Cold Spring Harbor Protocols

Volumn 2013, Issue 11, 2013, Pages 991-1005

  Livshits, Geulah ^a   Lowe, Scott W ^a,b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOUBLE STRANDED RNA; MESSENGER RNA; MICRORNA; RED FLUORESCENT PROTEIN; SHORT HAIRPIN RNA;

ANIMAL MODEL; ARTICLE; CANCER MODEL; EMBRYONIC STEM CELL; FLOW CYTOMETRY; GENE EXPRESSION; GENE MUTATION; GENE SILENCING; GENETICALLY ENGINEERED MOUSE STRAIN; HUMAN; IN VITRO GENE TRANSFER; MOUSE; NONHUMAN; RNA INTERFERENCE; TISSUE SPECIFICITY; TRANSGENE; ANIMAL; DISEASE MODEL; METHODOLOGY; NEOPLASM; PATHOLOGY; PATHOPHYSIOLOGY; REVIEW; TRANSGENIC MOUSE;

ANIMALS; DISEASE MODELS, ANIMAL; GENE KNOCKDOWN TECHNIQUES; MICE; MICE, TRANSGENIC; NEOPLASMS; RNA INTERFERENCE;

EID: 84887053305     PISSN: 19403402     EISSN: 15596095     Source Type: Journal    
DOI: 10.1101/pdb.top069856     Document Type: Article

References (112)

1. Agbunag C, Bar-Sagi D. 2004. Oncogenic K-ras drives cell cycle progression and phenotypic conversion of primary pancreatic duct epithelial cells. Cancer Res 64: 5659-5663.
2. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim Sungjoon, Wilson CJ, Lehár J, Kryukov GV, Sonkin D, et al. 2012. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483: 603-607.
3. Bartel DP. 2009. MicroRNAs: Target recognition and regulatory functions. Cell 136: 215-233.
4. Beard C, Hochedlinger K, Plath K, Wutz A, Jaenisch R. 2006. Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells. Genesis 44: 23-28.
5. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409: 363-366.
6. Beronja S, Livshits G, Williams S, Fuchs E. 2010. Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos. Nat Med 16: 821-827.
7. Bromberg-White JL, Webb CP, Patacsil VS, Miranti CK, Williams BO, Holmen SL. 2004. Delivery of short hairpin RNA sequences by using a replication-competent avian retroviral vector. J Virol 78: 4914-4916.
8. Brook FA, Gardner RL. 1997. The origin and efficient derivation of embryonic stem cells in the mouse. Proc Natl Acad Sci 94: 5709-5712.
9. Brummelkamp TR, Bernards R, Agami R. 2002a. A system for stable expression of short interferingRNAsin mammalian cells. Science 296: 550-553.
10. Brummelkamp TR, Bernards R, Agami R. 2002b. Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2: 243-247.
11. Cai X, Hagedorn CH, Cullen BR. 2004. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10: 1957-1966.
12. Cancer Genome Atlas Research Network. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474: 609-615.
13. Carmell MA, Zhang L, Conklin DS, Hannon GJ, Rosenquist TA. 2003. Germline transmission of RNAi in mice. Nat Struct Biol 10: 91-92.
14. Chang K, Elledge SJ, Hannon GJ. 2006. Lessons from Nature: MicroRNAbased shRNA libraries. Nat Meth 3: 707-714.
15. Chang L-Y, Lin Y-C, Mahalingam J, Huang C-T, Chen T-W, Kang C-W, Peng H-M, Chu Y-Y, Chiang J-M, Dutta A, et al. 2012. Tumor-derived chemokine CCL5 enhances TGF-β-mediated killing of CD8+ T cells in colon cancer by T-regulatory cells. Cancer Res 72: 1092-1102.
16. Cheng TL, Teng CF, Tsai WH, Yeh CW, Wu MP, Hsu HC, Hung CF, Chang WT. 2009. Multitarget therapy of malignant cancers by the head-to-tail tandem array multiple shRNAs expression system. Cancer Gene Ther 16: 516-531.
17. Chicas A, Wang X, Zhang C, McCurrach M, Zhao Z, Mert O, Dickins RA, Narita M, Zhang M, Lowe SW. 2010. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 17: 376-387.
18. Coumoul X, Shukla V, Li C, Wang R-H, Deng C-X. 2005. Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference. Nucleic Acids Res 33: e102.
19. Czauderna F, Santel A, Hinz M, Fechtner M, Durieux B, Fisch G, Leenders F, Arnold W, Giese K, Klippel A, et al. 2003. Inducible shRNA expression for application in a prostate cancer mouse model. Nucleic Acids Res 31: e127.
20. Denli AM, Tops BBJ, Plasterk RHA, Ketting RF, Hannon GJ. 2004. Processing of primary microRNAs by the Microprocessor complex. Nature 432: 231-235.
21. Dickins RA, Hemann MT, Zilfou JT, Simpson DR, Ibarra I, Hannon GJ, Lowe SW. 2005. Probing tumor phenotypes using stable and regulated synthetic microRNA precursors. Nat Genet 37: 1289-1295.
22. Dickins RA, McJunkin K, Hernando E, Premsrirut PK, Krizhanovsky V, Burgess DJ, Kim Sang Yong, Cordon-Cardo C, Zender L, Hannon GJ, et al. 2007. Tissue-specific and reversible RNA interference in transgenic mice. Nat Genet 39: 914-921.
23. Dow LE, Premsrirut PK, Zuber J, Fellmann C, McJunkin K, Miething C, Park Y, Dickins RA, Hannon GJ, Lowe SW. 2012. A pipeline for the generation of shRNA transgenic mice. Nat Protoc 7: 374-393.
24. Du Z, Podsypanina K, Huang S, McGrath A, Toneff MJ, Bogoslovskaia E, Zhang X, Moraes RC, Fluck M, Allred DC, et al. 2006. Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models. Proc Natl Acad Sci 103: 17396-17401.
25. DuPage M, Dooley AL, Jacks T. 2009. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat Protoc 4: 1064-1072.
26. Eakin GS, Hadjantonakis A-K. 2006. Production of chimeras by aggregation of embryonic stem cells with diploid or tetraploid mouse embryos. Nat Protoc 1: 1145-1153. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883166/.
27. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411: 494-498.
28. Evers B, Speksnijder EN, Schut E, Ciampricotti M, Smalley MJ, Derksen PWB, Jonkers J, de Visser KE. 2010. A tissue reconstitution model to study cancer cell-intrinsic and-extrinsic factors in mammary tumourigenesis. J Pathol 220: 34-44.
29. Fellmann C, Zuber J, McJunkin K, Chang K, Malone CD, Dickins RA, Xu Q, Hengartner MO, Elledge SJ, Hannon GJ, et al. 2011. Functional identification of optimized RNAi triggers using a massively parallel sensor assay. Mol Cell 41: 733-746.
30. Filipowicz W, Bhattacharyya SN, Sonenberg N. 2008. Mechanisms of posttranscriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet 9: 102-114.
31. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811.
32. Fletcher BS. 2010. Delivery of small interferingRNA (siRNA) using the sleeping beauty transposon. Cold Spring Harb Protoc 2010: pdb. prot5521.
33. Francia G, Cruz-Munoz W, Man S, Xu P, Kerbel RS. 2011. Mouse models of advanced spontaneous metastasis for experimental therapeutics. Nat Rev Cancer 11: 135-141.
34. Gil J, Esteban M. 2000. Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action. Apoptosis 5: 107-114.
35. Gilbert LA, Hemann MT. 2010. DNA damage-mediated induction of a chemoresistant niche. Cell 143: 355-366.
36. Gossen M, Freundlieb S, Bender G, Müller G, Hillen W, Bujard H. 1995. Transcriptional activation by tetracyclines in mammalian cells. Science 268: 1766-1769.
37. Gregory RI, Yan K-P, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. 2004. The Microprocessor complex mediates the genesis of microRNAs. Nature 432: 235-240.
38. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA. 2006. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441: 537-541.
39. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. 2001. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293: 1146-1150.
40. Hasuwa H, Kaseda K, Einarsdottir T, Okabe M. 2002. Small interfering RNA and gene silencing in transgenic mice and rats. FEBS Lett 532: 227-230.
41. Heggestad AD, Notterpek L, Fletcher BS. 2004. Transposon-based RNAi delivery system for generating knockdown cell lines. Biochem Biophys Res Commun 316: 643-650.
42. Hemann MT, Fridman JS, Zilfou JT, Hernando E, Paddison PJ, Cordon-Cardo C, Hannon GJ, Lowe SW. 2003. An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo. Nat Genet 33: 396-400.
43. Hitz C, Wurst W, Kühn R. 2007. Conditional brain-specific knockdown of MAPK using Cre/loxP regulated RNA interference. Nucleic Acids Res 35: e90.
44. Holmen SL. 2005. Essential role for ras signaling in glioblastoma maintenance. Cancer Res 65: 8250-8255.
45. Huijbers IJ, Krimpenfort P, Berns A, Jonkers J. 2011. Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse models. Bioessays 33: 701-710.
46. Hutvágner G, Zamore PD. 2002. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297: 2056-2060.
47. Hutvágner G, McLachlan J, Pasquinelli AE, Bálint E, Tuschl T, Zamore PD. 2001. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293: 834-838.
48. Jonkers J, Berns A. 2002. Conditional mouse models of sporadic cancer. Nat Rev Cancer 2: 251-265.
49. Kennerdell JR, Carthew RW. 1998. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell 95: 1017-1026.
50. Kunath T, Gish G, Lickert H, Jones N, Pawson T, Rossant J. 2003. Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype. Nat Biotechnol 21: 559-561.
51. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim Sunyoung, et al. 2003. The nuclear RNase III Drosha initiates micro-RNA processing. Nature 425: 415-419.
52. Lee Y, Kim M, Han J, Yeom K-H, Lee S, Baek SH, Kim VN. 2004. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23: 4051-4060.
53. Lewis BC, Chinnasamy N, Morgan RA, Varmus HE. 2001. Development of an avian leukosis-sarcoma virus subgroup A pseudotyped lentiviral vector. J Virol 75: 9339-9344.
54. Lewis BC, Klimstra DS, Varmus HE. 2003. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer. Genes Dev 17: 3127-3138.
55. Lewis BC, Klimstra DS, Socci ND, Xu S, Koutcher JA, Varmus HE. 2005. The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma. Mol Cell Biol 25: 1228-1237.
56. Lund AH, Duch M, Pedersen FS. 1996. Transcriptional silencing of retroviral vectors. J Biomed Sci 3: 365-378.
57. Luo J, Solimini NL, Elledge SJ. 2009. Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell 136: 823-837.
58. Ma J, Lanza DG, Guest I, Uk-Lim C, Glinskii A, Glinsky G, Sell S. 2012. Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model. Tumour Biol 33: 1983-1996.
59. Martin GR. 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci 78: 7634-7638.
60. Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, Verma IM. 2009. Development of a novel mouse glioma model using lentiviral vectors. Nat Med 15: 110-116.
61. Matsukura S, Jones PA, Takai D. 2003. Establishment of conditional vectors for hairpin siRNA knockdowns. Nucleic Acids Res 31: e77.
62. Matveeva OV, Kang Y, Spiridonov AN, Saetrom P, Nemtsov VA, Ogurtsov AY, Nechipurenko YD, Shabalina SA. 2010. Optimization of duplex stability and terminal asymmetry for shRNA design. PLoS One 5: e10180.
63. Meissner A, Eminli S, Jaenisch R. 2009. Derivation and manipulation of murine embryonic stem cells. Methods Mol Biol 482: 3-19.
64. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. 2004. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15: 185-197.
65. Moffat J, Grueneberg DA, Yang X, Kim So Young, Kloepfer AM, Hinkle G, Piqani B, Eisenhaure TM, Luo B, Grenier JK, et al. 2006. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124: 1283-1298.
66. Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC. 1993. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci 90: 8424-8428.
67. O'Gorman S, Fox DT, Wahl GM. 1991. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science 251: 1351-1355.
68. Oumard A, Qiao J, Jostock T, Li J, Bode J. 2006. Recommended method for chromosome exploitation: RMCE-based cassette-exchange systems in animal cell biotechnology. Cytotechnology 50: 93-108.
69. Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS. 2002. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 16: 948-958.
70. Paddison PJ, Silva JM, Conklin DS, Schlabach M, Li M, Aruleba S, Balija V, O'Shaughnessy A, Gnoj L, Scobie K, et al. 2004. A resource for large-scale RNA-interference-based screens in mammals. Nature 428: 427-431.
71. Persengiev SP, Zhu X, Green MR. 2004. Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10: 12-18.
72. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo H-K, Jang HG, Jha AK, et al. 2011. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476: 346-350.
73. Premsrirut PK, Dow LE, Kim Sang Yong, Camiolo M, Malone CD, Miething C, Scuoppo C, Zuber J, Dickins RA, Kogan SC, et al. 2011. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 145: 145-158.
74. Provenzano PP, Cuevas C, Chang AE, Goel VK, Hoff Von DD, Hingorani SR. 2012. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 21: 418-429.
75. Rao MK, Pham J, Imam JS, MacLean JA, Murali D, Furuta Y, Sinha-Hikim AP, Wilkinson MF. 2006. Tissue-specific RNAi reveals that WT1 ex-pression in nurse cells controls germ cell survival and spermatogenesis. Genes Dev 20: 147-152.
76. Raoul C, Abbas-Terki T, Bensadoun J-C, Guillot S, Haase G, Szulc J, Henderson CE, Aebischer P. 2005. Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nat Med 11: 423-428.
77. Reid SW, Tessarollo L. 2009. Isolation, microinjection and transfer of mouse blastocysts. Methods Mol Biol 530: 269-285.
78. Schlake T, Bode J. 1994. Use of mutated FLP recognition target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochemistry 33: 12746-12751.
79. Scuoppo C, Miething C, Lindqvist L, Reyes J, Ruse C, Appelmann I, Yoon S, Krasnitz A, Teruya-Feldstein J, Pappin D, et al. 2012. A tumour suppressor network relying on the polyamine-hypusine axis. Nature 487: 244-248.
80. Seibler J, Schübeler D, Fiering S, Groudine M, Bode J. 1998. DNA cassette exchange in ES cells mediated by Flp recombinase: An efficient strategy for repeated modification of tagged loci by marker-free constructs. Biochemistry 37: 6229-6234.
81. Seibler J, Kleinridders A, Küter-Luks B, Niehaves S, Brüning JC, Schwenk F. 2007. Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic Acids Res 35: e54.
82. Seidler B, Schmidt A, Mayr U, Nakhai H, Schmid RM, Schneider G, Saur D. 2008. A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors. Proc Natl Acad Sci 105: 10137-10142.
83. Sharpless NE, DePinho RA. 2006. The mighty mouse: Genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 5: 741-754.
84. Shi J, Wang E, Zuber J, Rappaport A, Taylor M, Johns C, Lowe SW, Vakoc CR. 2012. The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;NrasG12D acute myeloid leukemia. Oncogene 32: 930-938.
85. Silva JM, Li MZ, Chang Ken, Ge W, Golding MC, Rickles RJ, Siolas D, Hu G, Paddison PJ, Schlabach MR, et al. 2005. Second-generation shRNA libraries covering the mouse and human genomes. Nat Genet 37: 1281-1288.
86. Singh M, Lima A, Molina R, Hamilton P, Clermont AC, Devasthali V, Thompson JD, Cheng JH, Bou Reslan H, Ho CCK, et al. 2010. Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models. Nat Biotechnol 28: 585-593.
87. Singh M, Murriel CL, Johnson L. 2012. Genetically engineered mouse models: Closing the gap between preclinical data and trial outcomes. Cancer Res 72: 2695-2700.
88. Siwko SK, Bu W, Gutierrez C, Lewis B, Jechlinger M, Schaffhausen B, Li Y. 2008. Lentivirus-mediated oncogene introduction into mammary cells in vivo induces tumors. Neoplasia 10: 653.
89. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, et al. 2011. A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474: 337-342.
90. Stegmeier F, Hu G, Rickles RJ, Hannon GJ, Elledge SJ. 2005. A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells. Proc Natl Acad Sci 102: 13212-13217.
91. Suda T, Liu D. 2007. Hydrodynamic gene delivery: Its principles and applications. Mol Ther 15: 2063-2069.
92. Tinkle CL, Pasolli HA, Stokes N, Fuchs E. 2008. New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Proc Natl Acad Sci 105: 15405-15410.
93. Tiscornia G, Singer O, Ikawa M, Verma IM. 2003. A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proc Natl Acad Sci 100: 1844-1848.
94. Turan S, Kuehle J, Schambach A, Baum C, Bode J. 2010. Multiplexing RMCE: Versatile extensions of the Flp-recombinase-mediated cassette-exchange technology. J Mol Biol 402: 52-69.
95. Turan S, Galla M, Ernst E, Qiao J, Voelkel C, Schiedlmeier B, Zehe C, Bode J. 2011. Recombinase-mediated cassette exchange (RMCE): Traditional concepts and current challenges. J Mol Biol 407: 193-221.
96. Van den Haute C, Eggermont K, Nuttin B, Debyser Z, Baekelandt V. 2003. Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Hum Gene Ther 14: 1799-1807.
97. Ventura A, Meissner A, Dillon CP, McManus M, Sharp PA, Van Parijs L, Jaenisch R, Jacks T. 2004. Cre-lox-regulated conditional RNA interference from transgenes. Proc Natl Acad Sci 101: 10380-10385.
98. Wang Y, Lin L, Zheng C. 2012. Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis. Exp Mol Med 44: 177-190.
99. Watters JW, Cheng C, Majumder PK, Wang R, Yalavarthi S, Meeske C, Kong L, Sun W, Lin J, Heyer J, et al. 2009. De novo discovery of a γ-secretase inhibitor response signature using a novel in vivo breast tumor model. Cancer Res 69: 8949-8957.
100. Williams RL, Hilton DJ, Pease S, Willson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM. 1988. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336: 684-687.
101. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW. 2007. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445: 656-660.
102. Yekta S, Shih I-H, Bartel DP. 2004. MicroRNA-directed cleavage of HOXB8 mRNA. Science 304: 594-596.
103. Ying Q-L, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A. 2008. The ground state of embryonic stem cell self-renewal. Nature 453: 519-523.
104. Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, et al. 2006. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125: 1253-1267.
105. Zender L, Xue W, Zuber J, Semighini CP, Krasnitz A, Ma B, Zender P, Kubicka S, Luk JM, Schirmacher P, et al. 2008. An oncogenomicsbased in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell 135: 852-864.
106. Zeng Y, Wagner EJ, Cullen BR. 2002. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9: 1327-1333.
107. Zeng Y, Cai X, Cullen BR. 2005. Use of RNA polymerase II to transcribe artificial microRNAs. Meth Enzymol 392: 371-380.
108. Zhao X-Y, Lv Z, Li W, Zeng F, Zhou Q. 2010. Production of mice using iPS cells and tetraploid complementation. Nat Protoc 5: 963-971.
109. Zhou Y, Rideout WM, Zi T, Bressel A, Reddypalli S, Rancourt R, Woo J-K, Horner JW, Chin L, Chiu MI, et al. 2009. Chimeric mouse tumor models reveal differences in pathway activation between ERBB family and KRAS-dependent lung adenocarcinomas. Nat Biotechnol 28: 71-78. http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1595.html.
110. Zuber J, McJunkin K, Fellmann C, Dow LE, Taylor MJ, Hannon GJ, Lowe SW. 2010. Toolkit for evaluating genes required for proliferation and survival using tetracycline-regulated RNAi. Nat Biotechnol 29: 79-83.
111. Zuber J, Rappaport AR, Luo W, Wang E, Chen C, Vaseva AV, Shi J, Weissmueller S, Fellman C, Taylor MJ, et al. 2011a. An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated selfrenewal program as essential for leukemia maintenance. Genes Dev 25: 1628-1640.
112. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, et al. 2011b. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524-528.