Tetracycline-regulated mouse models of cancer

Cold Spring Harbor Protocols

Volumn 2014, Issue 10, 2014, Pages 1005-1022

  Yeh, Elizabeth S ^a,b   Vernon Grey, Ann ^a,b   Martin, Heather ^a,b   Chodosh, Lewis A ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL PROTEIN; BETA CATENIN; DIETHYLNITROSAMINE; DOPACHROME TAUTOMERASE; DOXYCYCLINE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; FIBROBLAST GROWTH FACTOR; K RAS PROTEIN; METHYLNITROSOUREA; MONOPHENOL MONOOXYGENASE; PROTEIN KINASE LKB1; PROTEIN P53; SECRETORY PROTEIN; SOMATOMEDIN C RECEPTOR; TETRACYCLINE; THYROGLOBULIN; TRANSFORMING GROWTH FACTOR BETA; UVOMORULIN; TRANSACTIVATOR PROTEIN;

ARTICLE; CANCER GROWTH; CANCER MODEL; CARCINOGENESIS; CELL POPULATION; CELL PROLIFERATION; CHROMOSOME TRANSLOCATION; DISEASE ASSOCIATION; DRUG BIOAVAILABILITY; DRUG PENETRATION; EPITHELIAL MESENCHYMAL TRANSITION; EPITHELIUM CELL; ESCHERICHIA COLI; EXPERIMENTAL MODEL; GENE DELETION; GENE DELIVERY SYSTEM; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENE SILENCING; GENETICALLY ENGINEERED MOUSE STRAIN; GLIOBLASTOMA; HUMAN; HUMAN CYTOMEGALOVIRUS; LIVER CELL CARCINOMA; LUNG ADENOCARCINOMA; LUNG CANCER; MAMMARY GLAND; MYELOID LEUKEMIA; NONHUMAN; ONCOGENE C MYC; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PROSTATITIS; REGULATORY SEQUENCE; SKIN CANCER; THYROID FOLLICLE CELL; TOXICITY; TRANSCRIPTION INITIATION; TUMOR SUPPRESSOR GENE; ANIMAL; BIOSYNTHESIS; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; MOUSE; NEOPLASM; OPERATOR GENE; TRANSGENE;

MAMMALIA; MUS MUSCULUS;

ANIMALS; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; HUMANS; MICE; NEOPLASMS; OPERATOR REGIONS, GENETIC; TETRACYCLINE; TRANS-ACTIVATORS; TRANSGENES;

EID: 84923920086     PISSN: 19403402     EISSN: 15596095     Source Type: Journal    
DOI: 10.1101/pdb.top069823     Document Type: Article

References (163)

1. Allen TD, Rodriguez EM, Jones KD, Bishop JM. 2011a. Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Res 71: 6010-6018.
2. Allen TD, Zhu CQ, Jones KD, Yanagawa N, Tsao MS, Bishop JM. 2011b. Interaction between MYC and MCL1 in the genesis and outcome of non-small-cell lung cancer. Cancer Res 71: 2212-2221.
3. Ascierto PA, De Maio E, Bertuzzi S, Palmieri G, Halaban R, Hendrix M, Kashani-sabet M, Ferrone S, Wang E, Cochran A, et al. 2011. Future perspectives in melanoma research. Meeting report from the “Melanoma Research: Abridge Naples-USA. Naples, December 6th-7th 2010”. J Transl Med 9: 32.
4. Bade LK, Goldberg JE, Dehut HA, Hall MK, Schwertfeger KL. 2011. Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor. J Cell Sci 124: 3106-3117.
5. Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, Sanchez V, Jee D, Polyak K, Prat A, et al. 2012. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc Natl Acad Sci 109: 221-226.
6. Baron U, Freundlieb S, Gossen M, Bujard H. 1995. Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res 23: 3605-3606.
7. Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, Arvanitis C, Attardi LD, Feng S, Ruebner B, et al. 2004. Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol 2: e332.
8. Beer AL, Heckel AH, Greenlee MW. 2008a. A motion illusion reveals mechanisms of perceptual stabilization. PLoS One 3: e2741.
9. Beer S, Komatsubara K, Bellovin DI, Kurobe M, Sylvester K, Felsher DW. 2008b. Hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis. PLoS One 3: e2493.
10. Belteki G, Haigh J, Kabacs N, Haigh K, Sison K, Costantini F, Whitsett J, Quaggin SE, Nagy A. 2005. Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction. Nucleic Acids Res 33: e51.
11. Berkovich I, Efrat S. 2001. Inducible and reversible p-cell autoimmunity and hyperplasia in transgenic mice expressing a conditional oncogene. Diabetes 50: 2260-2267.
12. Beverly LJ, Felsher DW, Capobianco AJ. 2005. Suppression of p53 by Notch in lymphomagenesis: Implications for initiation and regression. Cancer Res 65: 7159-7168.
13. Bitton-Worms K, Pikarsky E, Aronheim A. 2010. The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice. Mol Cancer 9: 54.
14. Bockamp E, Maringer M, Spangenberg C, Fees S, Fraser S, Eshkind L, Oesch F, Zabel B. 2002. Of mice and models: Improved animal models for biomedical research. Physiol Genomics 11: 115-132.
15. Boxer RB, Jang JW, Sintasath L, Chodosh LA. 2004. Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6: 577-586.
16. Cairo S, Armengol C, De Reynies A, Wei Y, Thomas E, Renard CA, Goga A, Balakrishnan A, Semeraro M, Gresh L, et al. 2008. Hepatic stem-like phenotype and interplay ofWnt/p-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14: 471-484.
17. Campbell CI, Moorehead RA. 2011. Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors. BMC Cancer 11: 480.
18. Cao Z, Fan-Minogue H, Bellovin DI, Yevtodiyenko A, Arzeno J, Yang Q, Gambhir SS, Felsher DW. 2011. MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase. Cancer Res 71: 2286-2297.
19. Cawthorne C, Swindell R, Stratford IJ, Dive C, Welman A. 2007. Comparison of doxycycline delivery methods for Tet-inducible gene expression in a subcutaneous xenograft model. J Biomol Techn 18: 120-123.
20. Ceteci F, Ceteci S, Karreman C, Kramer BW, Asan E, Gotz R, Rapp UR. 2007. Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-driven murine lung cancer. Cancer Cell 12: 145-159.
21. Chakravarty D, Santos E, Ryder M, Knauf JA, Liao XH, West BL, Bollag G, Kolesnick R, Thin TH, Rosen N, et al. 2011. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J Clin Invest 121: 4700-711.
22. Chen B, Wang YY, Shen Y, Zhang WN, He HY, Zhu YM, Chen HM, Gu CH, Fan X, Chen JM, et al. 2012. Newly diagnosed acute lymphoblastic leukemia in China (I): Abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries. Leukemia 26: 1608-1616.
23. Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O’Hagan R, Pantginis J, Zhou H, et al. 1999. Essential role for oncogenic Ras in tumour maintenance. Nature 400: 468-472.
24. Cho HC, Lai CY, Shao LE, Yu J. 2011. Identification of tumorigenic cells in Kras(G12D)-induced lung adenocarcinoma. Cancer Res 71: 7250-7258.
25. Collins MA, Bednar F, Zhang Y, Brisset JC, Galban S, Galban CJ, Rakshit S, Flannagan KS, Adsay NV, Pasca di Magliano M. 2012. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 122: 639-653.
26. Connelly L, Barham W, Onishko HM, Sherrill T, Chodosh LA, Blackwell TS, Yull FE. 2011. Inhibition of NF-k B activity in mammary epithelium increases tumor latency and decreases tumor burden. Oncogene 30: 1402-1412.
27. Cook RS, Garrett JT, Sanchez V, Stanford JC, Young C, Chakrabarty A, Rinehart C, Zhang Y, Wu Y, Greenberger L, et al. 2011. ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis. Cancer Res 71: 3941-3951.
28. Creamer BA, Triplett AA, Wagner KU. 2009. Longitudinal analysis of mam-mogenesis using a novel tetracycline-inducible mouse model and in vivo imaging. Genesis 47: 234-245.
29. Creamer BA, Sakamoto K, Schmidt JW, Triplett AA, Moriggl R, Wagner KU. 2010. Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1. Mol Cell Biol 30: 2957-2970.
30. Curtin JF, Candolfi M, Xiong W, Lowenstein PR, Castro MG. 2008. Turning the gene tap off; implications of regulating gene expression for cancer therapeutics. Mol Cancer Ther 7: 439-448.
31. D’Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, Cox JD, Ha SI, Belka GK, Golant A, et al. 2001. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7: 235-239.
32. Dance-Barnes ST, Kock ND, Floyd HS, Moore JE, Mosley LJ, D’Agostino RB Jr, Pettenati MJ, Miller MS. 2008. Effects of mutant human Ki-ras (G12C) gene dosage on murine lung tumorigenesis and signaling to its downstream effectors. Toxicol Appl Pharmacol 231: 77-84.
33. Dance-Barnes ST, Kock ND, Moore jE, Lin EY, Mosley LJ, D’Agostino RB Jr, McCoy TP, Townsend AJ, Miller MS. 2009. Lung tumor promotion by curcumin. Carcinogenesis 30: 1016-1023.
34. Dave V, Wert SE, Tanner T, Thitoff AR, Loudy DE, Whitsett JA. 2008. Conditional deletion of Pten causes bronchiolar hyperplasia. Am J Respir Cell Mol Biol 38: 337-345.
35. Debies MT, Gestl SA, Mathers JL, Mikse OR, Leonard TL, Moody SE, Chodosh LA, Cardiff RD, Gunther EJ. 2008. Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf/ p53 pathway lesions but not p16 Ink4a loss. J Clin Invest 118: 51-63.
36. Dickins RA, McJunkin K, Hernando E, Premsrirut PK, Krizhanovsky V, Burgess DJ, Kim SY, Cordon-Cardo C, Zender L, Hannon GJ, et al. 2007. Tissue-specific and reversible RNA interference in transgenic mice. Nat Genet 39: 914-921.
37. 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.
38. Druker BJ. 2002. Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML. Oncogene 21: 8541-8546.
39. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, et al. 2008. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14: 1351-1356.
40. Farazi PA, DePinho RA. 2006. Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer 6: 674-687.
41. Felsher DW, Bishop JM. 1999. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4: 199-207.
42. Fisher GH, Orsulic S, Holland E, Hively WP, Li Y, Lewis BC, Williams BO, Varmus HE. 1999. Development of a flexible and specific gene delivery system for production of murine tumor models. Oncogene 18: 5253-5260.
43. Fisher GH, Wellen SL, Klimstra D, Lenczowski JM, Tichelaar JW, Lizak MJ, Whitsett JA, Koretsky A, Varmus HE. 2001. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev 15: 3249-3262.
44. Floyd HS, Farnsworth CL, Kock ND, Mizesko MC, Little JL, Dance ST, Everitt J, Tichelaar J, Whitsett JA, Miller MS. 2005. Conditional expression of the mutant Ki-rasG12C allele results in formation ofbenign lung adenomas: Development of a novel mouse lung tumor model. Carcinogenesis 26: 2196-2206.
45. Floyd HS, Jennings-Gee JE, Kock ND, Miller MS. 2006. Genetic and epigenetic alterations in lung tumors from bitransgenic Ki-rasG12C expressing mice. Mol Carcinog 45: 506-517.
46. Franks SE, Campbell CI, Barnett EF, Siwicky MD, Livingstone J, Cory S, Moorehead RA. 2012. Transgenic IGF-IR overexpression induces mammary tumors with basal-like characteristics, whereas IGF-IR-in-dependent mammary tumors express a claudin-low gene signature. Oncogene 31: 3298-3309.
47. Frech MS, Halama ED, Tilli MT, Singh B, Gunther EJ, Chodosh LA, Flaws JA, Furth PA. 2005. Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Res 65: 681-685.
48. Galvez AS, Duran A, Linares JF, Pathrose P, Castilla EA, Abu-Baker S, Leitges M, Diaz-Meco MT, Moscat J. 2009. Protein kinase CZ represses the interleukin-6 promoter and impairs tumorigenesis in vivo. Mol Cell Biol 29: 104-115.
49. Glaros S, Cirrincione GM, Palanca A, Metzger D, Reisman D. 2008. Targeted knockout ofBRG1 potentiates lung cancer development. Cancer Res 68: 3689-3696.
50. Goga A, Yang D, Tward AD, Morgan DO, Bishop JM. 2007. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med 13: 820-827.
51. Gossen M, Bujard H. 1992. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci 89: 5547-5551.
52. Goverdhana S, Puntel M, Xiong W, Zirger JM, Barcia C, Curtin JF, Soffer EB, Mondkar S, King GD, Hu J, et al. 2005. Regulatable gene expression systems for gene therapy applications: Progress and future challenges. Mol Ther 12: 189-211.
53. Grachtchouk M, Pero J, Yang SH, Ermilov AN, Michael LE, Wang A, Wilbert D, Patel RM, Ferris J, Diener J, et al. 2011. Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations. J Clin Invest 121: 1768-1781.
54. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN, Larue L. 2003. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63: 2172-2178.
55. Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, Dubus P, Sandgren EP, Barbacid M. 2007. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11: 291-302.
56. Gunther EJ, Belka GK, Wertheim GB, Wang J, Hartman JL, Boxer RB, Chodosh LA. 2002. A novel doxycycline-inducible system for the transgenic analysis of mammary gland biology. FASEB J 16: 283-292.
57. Gunther EJ, Moody SE, Belka GK, Hahn Kt, Innocent N, Dugan KD, Cardiff RD, Chodosh LA. 2003. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev 17: 488-501.
58. Gupta S, McGrath B, Cavener DR. 2009. PERK regulates the proliferation and development of insulin-secreting p-cell tumors in the endocrine pancreas of mice. PloS One 4: e8008.
59. Hamilton A, Helgason GV, Schemionek M, Zhang B, Myssina S, Allan EK, Nicolini FE, Muller-Tidow C, Bhatia R, Brunton VG, et al. 2012. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood 119: 1501-1510.
60. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144: 646-674.
61. Hasan MT, Schonig K, Berger S, Graewe W, Bujard H. 2001. Long-term, noninvasive imaging of regulated gene expression in living mice. Genesis 29: 116-122.
62. Hecht SS, Kassie F, Hatsukami DK. 2009. Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers. Nat Rev Cancer 9: 476-488.
63. Hennighausen LG, Sippel AE. 1982. Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland. Eur J Biochem 125: 131-141.
64. Hennighausen L, Wall RJ, Tillmann U, Li M, Furth PA. 1995. Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system. J Cell Biochem 59: 463-472.
65. Hidalgo M. 2010. Pancreatic cancer. NEngl J Med 362: 1605-1617.
66. Holmen SL, Williams BO. 2005. Essential role for Ras signaling in glioblastoma maintenance. Cancer Res 65: 8250-8255.
67. Hruska KS, Tilli MT, Ren S, Cotarla I, Kwong T, Li M, Fondell JD, Hewitt JA, Koos RD, Furth PA, et al. 2002. Conditional over-expression of estrogen receptor alpha in a transgenic mouse model. Transgenic Res 11: 361-372.
68. Huettner CS, Koschmieder S, Iwasaki H, Iwasaki-Arai J, Radomska HS, Akashi K, Tenen DG. 2003. Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome. Blood 102: 3363-3370.
69. Huettner CS, Zhang P, Van Etten RA, Tenen DG. 2000. Reversibilityofacute B-cell leukaemia induced by BCR-ABL1. Nat Genet 24: 57-60.
70. Ivanovska I, Zhang C, Liu AM, Wong KF, Lee NP, Lewis P, Philippar U, Bansal D, Buser C, Scott M, et al. 2011. Gene signatures derived from a c-MET-driven liver cancer mouse model predict survival of patients with hepatocellular carcinoma. PLoS One 6: e24582.
71. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA. 2001. Analysis oflung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15: 3243-3248.
72. Jain M, Arvanitis C, Chu K, Dewey W, Leonhardt E, Trinh M, Sundberg CD, Bishop JM, Felsher DW. 2002. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297: 102-104.
73. Jang JW, Boxer RB, Chodosh LA. 2006. Isoform-specific ras activation and oncogene dependence during MYC-and Wnt-induced mammary tu-morigenesis. Mol Cell Biol 26: 8109-8121.
74. Jarde T, Evans RJ, McQuillan KL, Parry L, Feng GJ, Alvares B, Clarke AR, Dale TC. 2012. In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OAN89P-catenin system. Oncogene.
75. Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, et al. 2006a. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 9: 485-495.
76. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A, Jung BL, McNamara K, Xia H, Glatt KA, et al. 2006b. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci 103: 7817-7822.
77. Jones RA, Campbell CI, Gunther EJ, Chodosh LA, Petrik JJ, Khokha R, Moorehead RA. 2007. Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene 26: 1636-1644.
78. Jones RA, Campbell CI, Wood GA, Petrik JJ, Moorehead RA. 2009. Reversibility and recurrence of IGF-IR-induced mammary tumors. Oncogene 28: 2152-2162.
79. Kaposi-Novak P, Libbrecht L, Woo HG, Lee YH, Sears NC, Coulouarn C, Conner EA, Factor VM, Roskams T, Thorgeirsson SS. 2009. Central role of c-Myc during malignant conversion in human hepatocarcino-genesis. Cancer Res 69: 2775-2782.
80. Karlsson A, Giuriato S, Tang F, Fung-Weier J, Levan G, Felsher DW. 2003. Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations. Blood 101: 2797-2803.
81. Koschmieder S, Gottgens B, Zhang P, Iwasaki-Arai J, Akashi K, Kutok JL, Dayaram T, Geary K, Green AR, Tenen DG, et al. 2005. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood 105: 324-334.
82. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, et al. 2009. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137: 1005-1017.
83. Krestel HE, Mayford M, Seeburg PH, Sprengel R. 2001. A GFP-equipped bidirectional expression module well suited for monitoring tetracycline-regulated gene expression in mouse. Nucleic Acids Res 29: E39.
84. Land H, Parada LF, Weinberg RA. 1983. Tumorigenic conversion ofprimary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304: 596-602.
85. Lee SK, Kumar P. 2009. Conditional RNAi: Towards a silent gene therapy. Adv Drug Deliv Rev 61: 650-664.
86. Letai A, Sorcinelli MD, Beard C, Korsmeyer SJ. 2004. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell 6: 241-249.
87. Leung JY, Andrechek ER, Cardiff RD, Nevins JR. 2012. Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence. Oncogene 31: 2545-2554.
88. Lewandoski M. 2001. Conditional control of gene expression in the mouse. Nat Rev Genet 2: 743-755.
89. Li Z, Tognon CE, Godinho FJ, Yasaitis L, Hock H, Herschkowitz JI, Lannon CL, Cho E, Kim SJ, Bronson RT, et al. 2007. ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell 12: 542-558.
90. Li Y, Qu P, Wu L, Li B, Du H, Yan C. 2011. Api6/AIM/Spa/CD5L overexpression in alveolar type II epithelial cells induces spontaneous lung adenocarcinoma. Cancer Res 71: 5488-5499.
91. Linnerth NM, Siwicky MD, Campbell CI, Watson KL, Petrik JJ, Whitsett JA, Moorehead RA. 2009. Type I insulin-like growth factor receptor induces pulmonary tumorigenesis. Neoplasia 11: 672-682.
92. Liu P, Cheng H, Santiago S, Raeder M, Zhang F, Isabella A, Yang J, Semaan DJ, Chen C, Fox EA, et al. 2011. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med 17: 1116-1120.
93. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129-2139.
94. Mao J, Barrow J, McMahon J, Vaughan J, McMahon AP. 2005. An ES cell system for rapid, spatial and temporal analysis of gene function in vitro and in vivo. Nucleic Acids Res 33: e155.
95. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274: 1678-1683.
96. McHenry PR, Sears JC, Herrick MP, Chang P, Heckman-Stoddard BM, Rybarczyk M, Chodosh LA, Gunther EJ, Hilsenbeck SG, Rosen JM, et al.2010. P190BRhoGAPhaspro-tumorigenicfunctionsduringMMTV-Neumammarytumorigenesis and metastasis. Breast Cancer Res 12: R73.
97. Meuwissen R, Berns A. 2005. Mouse models for human lung cancer. Genes Dev 19: 643-664.
98. Miermont AM, Parrish AR, Furth PA. 2010. Role of ERalpha in the differential response of Stat5a loss in susceptibility to mammary preneoplasia and DMBA-induced carcinogenesis. Carcinogenesis 31: 1124-1131.
99. Minowada G, Miller YE. 2009. Overexpression of Sprouty 2 in mouse lung epithelium inhibits urethane-induced tumorigenesis. Am J Respir Cell Mol Biol 40: 31-37.
100. Miyazaki S, Miyazaki T, Tashiro F, Yamato E, Miyazaki J. 2005. Development of a single-cassette system for spatiotemporal gene regulation in mice. Biochem Biophys Res Commun 338: 1083-1088.
101. Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, Innocent N, Cardiff RD, Schnall MD, Chodosh LA. 2002. Conditional activation ofNeu in the mammaryepithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2: 451-461.
102. Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, Notorfrancesco KL, CardiffRD, Chodosh LA. 2005. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell 8: 197-209.
103. Munoz B, Bolander FF Jr. 1989. Prolactin regulation of mouse mammary tumor virus (MMTV) expression in normal mouse mammary epithelium. Mol Cell Endocrinol 62: 23-29.
104. Muraoka-Cook RS, Kurokawa H, Koh Y, Forbes JT, Roebuck LR, Barcellos-Hoff MH, Moody SE, Chodosh LA, Arteaga CL. 2004. Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors. Cancer Res 64: 9002-9011.
105. Nishijima H, Yasunari T, Nakayama T, Adachi N, Shibahara K. 2009. Improved applications ofthe tetracycline-regulated gene depletion system. Biosci Trends 3: 161-167.
106. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al. 2004. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304: 1497-1500.
107. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, et al. 2004. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci 101: 13306-13311.
108. Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H. 2008a. Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321: 1841-1844.
109. Podsypanina K, Politi K, Beverly LJ, Varmus HE. 2008b. Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proc Natl Acad Sci 105: 5242-5247.
110. Politi K, Zakowski MF, Fan PD, Schonfeld EA, Pao W, Varmus HE. 2006. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev 20: 1496-1510.
111. Pond AC, Herschkowitz JI, Schwertfeger KL, Welm B, Zhang Y, York B, Cardiff RD, Hilsenbeck S, Perou CM, Creighton CJ, et al. 2010. Fibroblast growth factor receptor signaling dramatically accelerates tumori-genesis and enhances oncoprotein translation in the mouse mammary tumorvirus-Wnt-1 mouse model ofbreast cancer. Cancer Res 70: 48684879.
112. Qu P, Du H, Wang X, Yan C. 2009. Matrix metalloproteinase 12 overexpression in lung epithelial cells plays a key role in emphysema to lung bron-chioalveolar adenocarcinoma transition. Cancer Res 69: 7252-7261.
113. Quere R, Andradottir S, Brun AC, Zubarev RA, Karlsson G, Olsson K, Magnusson M, Cammenga J, Karlsson S. 2011. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event. Leukemia 25: 515-526.
114. Rapp UR, Korn C, Ceteci F, Karreman C, Luetkenhaus K, Serafin V, Zanucco E, Castro I, Potapenko T. 2009. MYC is a metastasis gene for non-small-cell lung cancer. PLoS One 4: e6029.
115. Rauch DA, Ratner L.2011. Targeting HTLV-1 activation ofNFKB in mouse models and ATLL patients. Viruses 3: 886-900.
116. Reddy JP, Peddibhotla S, Bu W, Zhao J, Haricharan S, Du YC, Podsypanina K, Rosen JM, Donehower LA, Li Y. 2010. Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation. Proc Natl Acad Sci 107: 3728-3733.
117. Regales L, Balak MN, Gong Y, Politi K, Sawai A, Le C, Koutcher JA, Solit DB, Rosen N, Zakowski MF, et al. 2007. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. PLoS One 2: e810.
118. Reynaud D, Pietras E, Barry-Holson K, Mir A, Binnewies M, Jeanne M, Sala-Torra O, Radich JP, Passegue E. 2011. IL-6 controls leukemic multi-potent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell 20: 661-673.
119. Saddic LA, Wirt S, Vogel H, Felsher DW, Sage J. 2011. Functional interactions between retinoblastoma and c-MYC in a mouse model of hepatocellular carcinoma. PLoS One 6: e19758.
120. Sarkisian CJ, Keister BA, Stairs DB, Boxer RB, Moody SE, Chodosh LA. 2007. Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nat Cell Biol 9: 493-505.
121. Scaglioni PP, Yung TM, Cai LF, Erdjument-Bromage H, Kaufman AJ, Singh B, Teruya-Feldstein J, Tempst P, Pandolfi PP. 2006. A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell 126: 269-283.
122. Schonig K, Schwenk F, Rajewsky K, Bujard H. 2002. Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res 30: e134.
123. Schultze N, Burki Y, Lang Y, Certa U, Bluethmann H. 1996. Efficient control of gene expression by single step integration of the tetracycline system in transgenic mice. Nat Biotechnol 14: 499–503.
124. Sequist LV, Lynch TJ. 2008. EGFR tyrosine kinase inhibitors in lung cancer: An evolving story. Annu Rev Med 59: 429–442.
125. Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, et al. 2004. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431: 1112–1117.
126. Shaw AT, Meissner A, Dowdle JA, Crowley D, Magendantz M, Ouyang C, Parisi T, Rajagopal J, Blank LJ, Bronson RT, et al. 2007. Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis. Genes Dev 21: 694–707.
127. Shen Q, Uray IP, Li Y, Zhang Y, Hill J, Xu XC, Young MR, Gunther EJ, Hilsenbeck SG, Colburn NH, et al. 2008. Targeting the activator protein 1 transcription factor for the prevention of estrogen receptor-negative mammary tumors. Cancer Prev Res (Phila) 1: 45–55.
128. Simpson DS, Mason-Richie NA, Gettler CA, Wikenheiser-Brokamp KA. 2009. Retinoblastoma family proteins have distinct functions in pulmonary epithelial cells in vivo critical for suppressing cell growth and tumorigenesis. Cancer Res 69: 8733–8741.
129. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. 2001. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783–792.
130. Sotillo R, Schvartzman JM, Socci ND, Benezra R. 2010. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 464: 436–440.
131. Stein TJ, Jochem A, Holmes KE, Sandgren EP. 2011. Effect of mutant β- catenin on liver growth homeostasis and hepatocarcinogenesis in transgenic mice. Liver Int 31: 303–312.
132. Thorgeirsson SS, Grisham JW. 2002. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31: 339–346.
133. Tichelaar JW, Lu W, Whitsett JA. 2000. Conditional expression of fibroblast growth factor-7 in the developing and mature lung. J Biol Chem 275: 11858–11864.
134. Tilli MT, Frech MS, Steed ME, Hruska KS, Johnson MD, Flaws JA, Furth PA. 2003. Introduction of estrogen receptor-alpha into the tTA/TAg conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma. Am J Pathol 163: 1713–1719.
135. Tran PT, Fan AC, Bendapudi PK, Koh S, Komatsubara K, Chen J, Horng G, Bellovin DI, Giuriato S, Wang CS, et al. 2008. Combined inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS One 3: e2125.
136. Tran PT, Bendapudi PK, Lin HJ, Choi P, Koh S, Chen J, Horng G, Hughes NP, Schwartz LH, Miller VA, et al. 2011. Survival and death signals can predict tumor response to therapy after oncogene inactivation. Sci Transl Med 3: 103ra199.
137. Trimboli AJ, Fukino K, de Bruin A, Wei G, Shen L, Tanner SM, Creasap N, Rosol TJ, Robinson ML, Eng C, et al. 2008. Direct evidence for epithelial- mesenchymal transitions in breast cancer. Cancer Res 68: 937–945.
138. Urlinger S, Baron U, Thellmann M, Hasan MT, Bujard H, Hillen W. 2000. Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity. Proc Natl Acad Sci 97: 7963–7968.
139. Utomo AR, Nikitin AY, Lee WH. 1999. Temporal, spatial, and cell typespecific control of Cre-mediated DNA recombination in transgenic mice. Nat Biotechnol 17: 1091–1096.
140. Vanbrocklin MW, Robinson JP, Lastwika KJ, McKinney AJ, Gach HM, Holmen SL. 2012. Ink4a/Arf loss promotes tumor recurrence following Ras inhibition. Neuro Oncol 14: 34–42.
141. Vitale-Cross L, Amornphimoltham P, Fisher G, Molinolo AA, Gutkind JS. 2004. Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis. Cancer Res 64: 8804–8807.
142. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, et al. 2002. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20: 719–726.
143. Wang R, Ferrell LD, Faouzi S, Maher JJ, Bishop JM. 2001. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol 153: 1023–1034.
144. Wang Z, Rao DD, Senzer N, Nemunaitis J. 2011. RNA interference and cancer therapy. Pharm Res 28: 2983–2995.
145. Weinstein IB. 2002. Cancer. Addiction to oncogenes–the Achilles heal of cancer. Science 297: 63–64.
146. Welm BE, Freeman KW, Chen M, Contreras A, Spencer DM, Rosen JM. 2002. Inducible dimerization of FGFR1: Development of a mouse model to analyze progressive transformation of the mammary gland. J Cell Biol 157: 703–714.
147. Welm AL, Kim S, Welm BE, Bishop JM. 2005. MET and MYC cooperate in mammary tumorigenesis. Proc Natl Acad Sci 102: 4324–4329.
148. Weng Y, Fang C, Turesky RJ, Behr M, Kaminsky LS, Ding X. 2007. Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductase-null mice. Cancer Res 67: 7825–7832.
149. Whitsett JA, Glasser SW, Tichelaar JW, Perl AK, Clark JC, Wert SE. 2001. Transgenic models for study of lung morphogenesis and repair: Parker B. Francis lecture. Chest 120: 27S–30S.
150. Wiesner SM, Jones JM, Hasz DE, Largaespada DA. 2005. Repressible transgenic model of NRAS oncogene-driven mast cell disease in the mouse. Blood 106: 1054–1062.
151. Woodard LE, Keravala A, Jung WE, Wapinski OL, Yang Q, Felsher DW, Calos MP. 2010. Impact of hydrodynamic injection and φC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma. PLoS One 5: e11367.
152. Woods SL, Bishop JM. 2011. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter. Transgenic Res 20: 421–428.
153. Xie W, Chow LT, Paterson AJ, Chin E, Kudlow JE. 1999. Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFα expression in transgenic mice. Oncogene 18: 3593–3607.
154. Yanagi S, Kishimoto H, Kawahara K, Sasaki T, Sasaki M, Nishio M, Yajima N, Hamada K, Horie Y, Kubo H, et al. 2007. Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice. J Clin Invest 117: 2929–2940.
155. Yang J, Splittgerber R, Yull FE, Kantrow S, Ayers GD, Karin M, Richmond A. 2010. Conditional ablation of Ikkb inhibits melanoma tumor development in mice. J Clin Invest 120: 2563–2574.
156. Yeh ES, Yang TW, Jung JJ, Gardner HP, Cardiff RD, Chodosh LA. 2011. Hunk is required for HER2/neu-induced mammary tumorigenesis. J Clin Invest 121: 866–879.
157. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, et al. 2012. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149: 656–670.
158. Young RM, Polsky A, Refaeli Y. 2009. TC-PTP is required for the maintenance of MYC-driven B-cell lymphomas. Blood 114: 5016–5023.
159. Yu HM, Liu B, Chiu SY, Costantini F, Hsu W. 2005. Development of a unique system for spatiotemporal and lineage-specific gene expression in mice. Proc Natl Acad Sci 102: 8615–8620.
160. Zabala M, Wang L, Hernandez-Alcoceba R, Hillen W, Qian C, Prieto J, Kramer MG. 2004. Optimization of the Tet-on system to regulate interleukin 12 expression in the liver for the treatment of hepatic tumors. Cancer Res 64: 2799–2804.
161. Zeng X, Shaikh FY, Harrison MK, Adon AM, Trimboli AJ, Carroll KA, Sharma N, Timmers C, Chodosh LA, Leone G, et al. 2010. The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. Oncogene 29: 5103–5112.
162. Zhang Q, Triplett AA, Harms DW, Lin WC, Creamer BA, Rizzino A, Wagner KU. 2010. Temporally and spatially controlled expression of transgenes in embryonic and adult tissues. Transgenic Res 19: 499–509.
163. Zhang X, Pfeiffer HK, Mellert HS, Stanek TJ, Sussman RT, Kumari A, Yu D, Rigoutsos I, Thomas-Tikhonenko A, Seidel HE, et al. 2011. Inhibition of the single downstream target BAG1 activates the latent apoptotic potential of MYC. Moll Cell Biol 31: 5037–5045.