Maximizing mouse cancer models

Nature Reviews Cancer

Volumn 7, Issue 9, 2007, Pages 645-658

  Frese, Kristopher K ^a   Tuveson, David A ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL PROTEIN; COMPLEMENTARY DNA; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; GREEN FLUORESCENT PROTEIN; HEAT SHOCK PROTEIN; K RAS PROTEIN; MYC PROTEIN; TELOMERASE;

ALLELE; BIOSTATISTICS; CANCER DIAGNOSIS; CANCER GENETICS; CANCER MODEL; CARCINOGENESIS; ENVIRONMENTAL EXPOSURE; GENE EXPRESSION; GENE STRUCTURE; GENE TARGETING; GENOMIC INSTABILITY; GENOMICS; GLYCOSYLATION; HETEROZYGOSITY LOSS; HUMAN; IMMUNE SYSTEM; LIGAND BINDING; NONHUMAN; ONCOGENE H RAS; PRIORITY JOURNAL; PROTEIN FOLDING; REVIEW; SOLID TUMOR; SOMATIC MUTATION; TELOMERE; TUMOR SUPPRESSOR GENE;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; DISEASE MODELS, ANIMAL; GENES, TUMOR SUPPRESSOR; HUMANS; MEDICAL ONCOLOGY; MICE; MICE, TRANSGENIC; MODELS, ANIMAL; NEOPLASM TRANSPLANTATION; NEOPLASMS; ONCOGENES;

EID: 34548217651     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2192     Document Type: Review

References (201)

1. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000).
2. Kendall, S. D., Adam, S. J. & Counter, C. M. Genetically engineered human cancer models utilizing mammalian transgene expression. Cell Cycle 5, 1074-1079 (2006).
3. Lock, R. B. et al. The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse. Blood 99, 4100-4108 (2002).
4. Rubio-Viqueira, B. et al. An in vivo platform for translational drug development in pancreatic cancer. Clin. Cancer Res 12, 4652-4661 (2006).
5. Sikder, H. et al. Disruption of Id1 reveals major differences in angiogenesis between transplanted and autochthonous tumors. Cancer Cell 4, 291-299 (2003).
6. Becher, O. J. & Holland, E. C. Genetically engineered models have advantages over xenografts for preclinical studies. Cancer Res. 66, 3355-3358 (2006).
7. De Both, N. J., Vermey, M., Groen, N., Dinjens, W. N. & Bosman, F. T. Clonal growth of colorectal-carcinoma cell lines transplanted to nude mice. Int. J. Cancer 72, 1137-1141 (1997).
8. Staroselsky, A. N. et al. The use of molecular genetic markers to demonstrate the effect of organ environment on clonal dominance in a human renal-cell carcinoma grown in nude mice. Int. J. Cancer 51, 130-138 (1992).
9. Kang, Y. et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3, 537-549 (2003).
10. Johnson, J. I. et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br. J. Cancer 84, 1424-1431 (2001).
11. Fiebig, H. H., Berger, D. P., Winterhalter, B. R. & Plowman, J. In vitro and in vivo evaluation of US-NCI compounds in human tumor xenografts. Cancer Treat. Rev. 17, 109-117 (1990).
12. Hardisty, J. F. Factors influencing laboratory animal spontaneous tumor profiles. Toxicol. Pathol. 13, 95-104 (1985).
13. van Kranen, H. J. et al. Frequent p53 alterations but low incidence of ras mutations in UV-B-induced skin tumors of hairless mice. Carcinogenesis 16, 1141-1147 (1995).
14. Balmain, A. & Pragnell, I. B. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303, 72-74 (1983).
15. Cardiff, R. D. & Kenney, N. Mouse mammary tumor biology: a short history. Adv. Cancer Res. 98, 53-116 (2007).
16. Enno, A. et al. MALToma-like lesions in the murine gastric mucosa after long-term infection with Helicobacter felis. A mouse model of Helicobacter pylori-induced gastric lymphoma. Am. J. Pathol. 147, 217-222 (1995).
17. Jonkers, J. & Berns, A. Conditional mouse models of sporadic cancer. Nature Rev. Cancer 2, 251-265 (2002).
18. Tuveson, D. A. & Jacks, T. Technologically advanced cancer modeling in mice. Curr. Opin. Genet. Dev. 12, 105-110 (2002).
19. Gannon, M., Gamer, L. W. & Wright, C. V. Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. Dev. Biol. 238, 185-201 (2001).
20. Mattick, J. S. & Makunin, I. V. Non-coding RNA. Hum. Mol. Genet. 15 Spec. No 1, R17-R29 (2006).
21. Robertson, G. et al. Position-dependent variegation of globin transgene expression in mice. Proc. Natl Acad. Sci. USA 92, 5371-5375 (1995).
22. Palomo, C., Zou, X., Nicholson, I. C., Butzler, C. & Bruggemann, M. B-cell tumorigenesis in mice carrying a yeast artificial chromosome-based immunoglobulin heavy/c-myc translocus is independent of the heavy chain intron enhancer (Emu). Cancer Res. 59, 5625-5628 (1999).
23. Kaufman, R. M., Pham, C. T. & Ley, T. J. Transgenic analysis of a 100-kb human β-globin cluster-containing DNA fragment propagated as a bacterial artificial chromosome. Blood 94, 3178-3184 (1999).
24. Schonig, K., Schwenk, F., Rajewsky, K. & Bujard, H. Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res. 30, e134 (2002).
25. Kuhn, R., Schwenk, F., Aguet, M. & Rajewsky, K. Inducible gene targeting in mice. Science 269, 1427-1429 (1995).
26. Weinstein, I. B. Cancer. Addiction to oncogenes - the Achilles heal of cancer. Science 297, 63-64 (2002).
27. Chin, L. et al. Essential role for oncogenic Ras in tumour maintenance. Nature 400, 468-472 (1999). The first mouse solid tumour models to experimentally demonstrate a requirement for oncogene expression in tumour maintenance.
28. Fisher, G. H. et al. 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 (2001).
29. Felsher, D. W. & Bishop, J. M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4, 199-207 (1999).
30. Huettner, C. S., Zhang, P., Van Etten, R. A. & Tenen, D. G. Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nature Genet. 24, 57-60 (2000).
31. Moody, S. E. et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2, 451-461 (2002).
32. G12V expression promotes proliferation. It also raises the concern that inducible ectopic oncogenes (and constitutive ectopic oncogenes) may inadvertently cause a non-physiological toxic response in cells in vivo.
33. Blakely, C. M. et al. Developmental stage determines the effects of MYC in the mammary epithelium. Development 132, 1147-1160 (2005).
34. Blyth, K. et al. Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycER mice. Oncogene 19, 773-782 (2000).
35. Martins, C. P., Brown-Swigart, L. & Evan, G. I. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 127, 1323-1334 (2006).
36. Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665 (2007).
37. Rusk, N. Making mice at high speed. Nature Methods 4, 196-197 (2007).
38. Holland, E. C., Hively, W. P., DePinho, R. A. & Varmus, H. E. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev. 12, 3675-3685 (1998).
39. Orsulic, S. et al. Induction of ovarian cancer by defined multiple genetic changes in a mouse model system. Cancer Cell 1, 53-62 (2002).
40. Lewis, B. C., Klimstra, D. S. & Varmus, H. E. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer. Genes Dev. 17, 3127-3138 (2003).
41. Lewis, B. C. et al. The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma. Mol. Cell Biol. 25, 1228-1237 (2005).
42. Lewis, B. C., Chinnasamy, N., Morgan, R. A. & Varmus, H. E. Development of an avian leukosis-sarcoma virus subgroup A pseudotyped lentiviral vector. J. Virol. 75, 9339-9344 (2001).
43. Theodorou, V. et al. MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nature Genet. 39, 759-769 (2007).
44. Thomas, K. R. & Capecchi, M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503-512 (1987).
45. Cichowski, K. et al. Mouse models of tumor development in neurofibromatosis type 1. Science 286, 2172-2176 (1999).
46. Clarke, A. R. et al. Requirement for a functional Rb-1 gene in murine development. Nature 359, 328-330 (1992).
47. Jacks, T. et al. Effects of an Rb mutation in the mouse. Nature 359, 295-300 (1992).
48. Lee, E. Y. et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359, 288-294 (1992).
49. Lakso, M. et al. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc. Natl Acad. Sci. USA 89, 6232-6236 (1992).
50. Rubin, B. P. et al. A knock-in mouse model of gastrointestinal stromal tumor harboring kit K641E. Cancer Res. 65, 6631-6639 (2005).
51. Sotillo, R. et al. Invasive melanoma in Cdk4-targeted mice. Proc. Natl Acad. Sci. USA 98, 13312-13317 (2001).
52. Tuveson, D. A. et al. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 5, 375-387 (2004).
53. Schubbert, S. et al. Germline KRAS mutations cause Noonan syndrome. Nature Genet. 38, 331-336 (2006).
54. de Alboran, I. M. et al. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14, 45-55 (2001).
55. Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243-3248 (2001).
56. Lewandoski, M. & Martin, G. R. Cre-mediated chromosome loss in mice. Nature Genet. 17, 223-225 (1997).
57. Dewald, G. W., Noel, P., Dahl, R. J. & Spurbeck, J. L. Chromosome abnormalities in malignant hematologic disorders. Mayo Clin. Proc. 60, 675-689 (1985).
58. Mitelman, F., Johansson, B. & Mertens, F. The impact of translocations and gene fusions on cancer causation. Nature Rev. Cancer 7, 233-245 (2007).
59. Smith, A. J., Xian, J., Richardson, M., Johnstone, K. A. & Rabbitts, P. H. Cre-loxP chromosome engineering of a targeted deletion in the mouse corresponding to the 3p21. 3 region of homozygous loss in human tumours. Oncogene 21, 4521-4529 (2002).
60. Kmita, M., Kondo, T. & Duboule, D. Targeted inversion of a polar silencer within the HoxD complex re-allocates domains of enhancer sharing. Nature Genet. 26, 451-454 (2000).
61. Langer, S. J., Ghafoori, A. P., Byrd, M. & Leinwand, L. A genetic screen identifies novel non-compatible loxP sites. Nucleic Acids Res. 30, 3067-3077 (2002).
62. Forster, A. et al. Engineering de novo reciprocal chromosomal translocations associated with Mll to replicate primary events of human cancer. Cancer Cell 3, 449-458 (2003).
63. Johnson, L. et al. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 410, 1111-1116 (2001). Describes the generation of a stochastic model for lung cancer that accurately mimics the mutation of a single cell in the context of normal surrounding tissue.
64. Coste, I., Freund, J. N., Spaderna, S., Brabletz, T. & Renno, T. Precancerous lesions upon sporadic activation of β-catenin in mice. Gastroenterology 132, 1299-1308 (2007).
65. Rudolph, K. L. et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701-712 (1999).
66. Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527-538 (1999). References 65 and 66 demonstrate that mutation of telomerase predisposes mice to cancers that exhibit genomic instability, a hallmark of human cancers.
67. Seibler, J. et al. Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic Acids Res. 35, e54 (2007).
68. Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660 (2007).
69. Kumar, M. S., Lu, J., Mercer, K. L., Golub, T. R. & Jacks, T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nature Genet. 39, 673-677 (2007).
70. Collier, L. S., Carlson, C. M., Ravimohan, S., Dupuy, A. J. & Largaespada, D. A. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature 436, 272-276 (2005).
71. Dupuy, A. J., Akagi, K., Largaespada, D. A., Copeland, N. G. & Jenkins, N. A. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature 436, 221-226 (2005). References 70 and 71 report the use of a genetically encoded transposon-based mutagenesis system to perform forward genetic screens in mice.
72. Grippo, P. J., Nowlin, P. S., Demeure, M. J., Longnecker, D. S. & Sandgren, E. P. Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice. Cancer Res. 63, 2016-2019 (2003).
73. Guerra, C. et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11, 291-302 (2007).
74. Cohen, S. J. et al. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J. Clin. Oncol. 21, 1301-1306 (2003).
75. Kohl, N. E. et al. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nature Med. 1, 792-797 (1995).
76. Bos, J. L. ras oncogenes in human cancer: a review. Cancer Res. 49, 4682-4689 (1989).
77. Lerner, E. C., Qian, Y., Hamilton, A. D. & Sebti, S. M. Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor. J. Biol. Chem. 270, 26770-26773 (1995).
78. Majumder, P. K. & Sellers, W. R. Akt-regulated pathways in prostate cancer. Oncogene 24, 7465-7474 (2005).
79. Shen, W. H. et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128, 157-170 (2007).
80. James, R. M. et al. K-ras proto-oncogene exhibits tumor suppressor activity as its absence promotes tumorigenesis in murine teratomas. Mol. Cancer Res. 1, 820-825 (2003).
81. Zhang, Z. et al. Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nature Genet. 29, 25-33 (2001).
82. Bayascas, J. R., Sakamoto, K., Armit, L., Arthur, J. S. & Alessi, D. R. Evaluation of approaches to generation of tissue-specific knock-in mice. J. Biol. Chem. 281, 28772-28781 (2006).
83. Forster, A. et al. The invertor knock-in conditional chromosomal translocation mimic. Nature Methods 2, 27-30 (2005).
84. Dankort, D. et al. A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev. 21, 379-384 (2007). An excellent example of a conditional oncogene mouse model in which the animal is functionally wild type before induction of the mutation.
85. Oberdoerffer, P., Otipoby, K. L., Maruyama, M. & Rajewsky, K. Unidirectional Cre-mediated genetic inversion in mice using the mutant loxP pair lox66/ lox71. Nucleic Acids Res. 31, e140 (2003).
86. Zhang, Z. & Lutz, B. Cre recombinase-mediated inversion using lox66 and lox71: method to introduce conditional point mutations into the CREB-binding protein. Nucleic Acids Res. 30, e90 (2002).
87. Olive, K. P. et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119, 847-860 (2004).
88. Song, H., Hollstein, M. & Xu, Y. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nature Cell Biol. 9, 573-580 (2007).
89. Ahmed, B. Y. et al. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors. BMC Neurosci. 5, 4 (2004).
90. Vooijs, M., Jonkers, J. & Berns, A. A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP recombination is position dependent. EMBO Rep. 2, 292-297 (2001).
91. Kemp, R. et al. Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity. Nucleic Acids Res. 32, e92 (2004). A mouse model in which Cre activity is regulated at both the transcriptional and translational level, therefore preventing the background recombination associated with other inducible Cre models.
92. Hameyer, D. et al. Toxicity of ligand-dependant Cre-recombinases and generation of a conditional Cre-deleter mouse allowing mosaic recombination in peripheral tissues. Physiol. Genomics 12 June 2007 (doi:10. 1152/physiolgenomics. 00019. 2007)
93. Bjerkvig, R., Tysnes, B. B., Aboody, K. S., Najbauer, J. & Terzis, A. J. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nature Rev. Cancer 5, 899-904 (2005).
94. Peto, R. in Origins of Human Cancer 1403-1428 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1977) (eds Hiett, H. H., Watson, J. D & Winsten, J. A.).
95. Ijichi, H. et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 20, 3147-3160 (2006).
96. Izeradjene, K. et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 11, 229-243 (2007).
97. Hruban, R. H., Wilentz, R. E. & Kern, S. E. Genetic progression in the pancreatic ducts. Am. J. Pathol. 156, 1821-1825 (2000).
98. Kondo, S. et al. Efficient sequential gene regulation via FLP-and Cre-recombinase using adenovirus vector in mammalian cells including mouse ES cells. Microbiol. Immunol. 50, 831-843 (2006).
99. Rangarajan, A. & Weinberg, R. A. Opinion: Comparative biology of mouse versus human cells: modelling human cancer in mice. Nature Rev. Cancer 3, 952-959 (2003).
100. McClatchey, A. I. et al. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12, 1121-1133 (1998).
101. Trofatter, J. A. et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72, 791-800 (1993).
102. Giovannini, M. et al. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev. 14, 1617-1630 (2000).
103. Liu, K. et al. Recombinase-mediated cassette exchange to rapidly and efficiently generate mice with human cardiac sodium channels. Genesis 44, 556-564 (2006).
104. Zhuang, Y., Barndt, R. J., Pan, L., Kelley, R. & Dai, M. Functional replacement of the mouse E2A gene with a human HEB cDNA. Mol. Cell Biol. 18, 3340-3349 (1998).
105. Wallace, H. A. et al. Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell 128, 197-209 (2007). An example of recombinase-mediated cassette exchange in which a large human genomic region was introduced into the syntenic mouse locus to elicit a disease phenotype that accurately mimics the human condition.
106. Kipling, D. & Cooke, H. J. Hypervariable ultra-long telomeres in mice. Nature 347, 400-402 (1990).
107. Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460 (1990).
108. Prowse, K. R. & Greider, C. W. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc. Natl Acad. Sci. USA 92, 4818-4822 (1995).
109. Lee, H. W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569-574 (1998).
110. Ding, H. et al. Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein. Cell 117, 873-886 (2004).
111. Martignoni, M., Groothuis, G. M. & de Kanter, R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin. Drug Metab. Toxicol. 2, 875-894 (2006).
112. Gonzalez, F. J. & Kimura, S. Study of P450 function using gene knockout and transgenic mice. Arch. Biochem. Biophys. 409, 153-158 (2003).
113. Gonzalez, F. J. Cytochrome P450 humanised mice. Hum. Genomics 1, 300-306 (2004).
114. Xie, W. & Evans, R. M. Pharmaceutical use of mouse models humanized for the xenobiotic receptor. Drug Discov. Today 7, 509-515 (2002).
115. Corchero, J. et al. The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4α on the disposition of debrisoquine in the mouse. Mol. Pharmacol. 60, 1260-1267 (2001).
116. Granvil, C. P. et al. Expression of the human CYP3A4 gene in the small intestine of transgenic mice: in vitro metabolism and pharmacokinetics of midazolam. Drug Metab. Dispos. 31, 548-558 (2003).
117. Gonzalez, F. J. & Yu, A. M. Cytochrome P450 and xenobiotic receptor humanized mice. Annu. Rev. Pharmacol. Toxicol. 46, 41-64 (2006). An excellent review of currently available transgenic mice expressing human metabolic enzymes.
118. Bui, J. D. & Schreiber, R. D. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr. Opin. Immunol. 19, 203-208 (2007).
119. de Visser, K. E., Eichten, A. & Coussens, L. M. Paradoxical roles of the immune system during cancer development. Nature Rev. Cancer 6, 24-37 (2006).
120. Shultz, L. D., Ishikawa, F. & Greiner, D. L. Humanized mice in translational biomedical research. Nature Rev. Immunol. 7, 118-130 (2007).
121. Chang, C. H., Fodor, W. L. & Flavell, R. A. Reactivation of a major histocompatibility complex class II gene in mouse plasmacytoma cells and mouse T cells. J. Exp. Med. 176, 1465-1469 (1992).
122. Rehli, M. Of mice and men: species variations of Toll-like receptor expression. Trends Immunol. 23, 375-8 (2002).
123. Hayakawa, Y., Huntington, N. D., Nutt, S. L. & Smyth, M. J. Functional subsets of mouse natural killer cells. Immunol. Rev. 214, 47-55 (2006).
124. Chen, Z. et al. A 320-kilobase artificial chromosome encoding the human HLA DR3-DQ2 MHC haplotype confers HLA restriction in transgenic mice. J. Immunol. 168, 3050-3056 (2002).
125. Chen, Z. et al. Humanized transgenic mice expressing HLA DR4-DQ3 haplotype: reconstitution of phenotype and HLA-restricted T-cell responses. Tissue Antigens 68, 210-219 (2006).
126. Madsen, L. et al. Mice lacking all conventional MHC class II genes. Proc. Natl Acad. Sci. USA 96, 10338-10343 (1999).
127. Kobata, A. The third chains of living organisms-a trail of glycobiology that started from the third floor of building 4 in NIH. Arch. Biochem. Biophys. 426, 107-121 (2004).
128. Raju, T. S., Briggs, J. B., Borge, S. M. & Jones, A. J. Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology 10, 477-486 (2000).
129. Carpelan-Holmstrom, M., Louhimo, J., Stenman, U. H., Alfthan, H. & Haglund, C. CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers. Anticancer Res. 22, 2311-2316 (2002).
130. Gion, M. et al. CA27. 29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases. Eur. J. Cancer 37, 355-363 (2001).
131. Gadducci, A. et al. Serum half-life of CA 125 during early chemotherapy as an independent prognostic variable for patients with advanced epithelial ovarian cancer: results of a multicentric Italian study. Gynecol. Oncol. 58, 42-47 (1995).
132. Falk, P. G., Bry, L., Holgersson, J. & Gordon, J. I. Expression of a human alpha-1, 3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Leb-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection. Proc. Natl Acad. Sci. USA 92, 1515-1519 (1995).
133. Houghton, J. & Wang, T. C. Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 128, 1567-1578 (2005).
134. Itzkowitz, S. H. & Yio, X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G7-G17 (2004).
135. Seitz, H. K. & Stickel, F. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol. Chem. 387, 349-360 (2006).
136. Jura, N., Archer, H. & Bar-Sagi, D. Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between. Cell Res. 15, 72-77 (2005).
137. Engle, S. J. et al. Elimination of colon cancer in germ-free transforming growth factor β 1-deficient mice. Cancer Res. 62, 6362-6366 (2002).
138. Coussens, L. M., Tinkle, C. L., Hanahan, D. & Werb, Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103, 481-490 (2000).
139. de Visser, K. E., Korets, L. V. & Coussens, L. M. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7, 411-423 (2005).
140. Olumi, A. F. et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59, 5002-5011 (1999).
141. Orimo, A. et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121, 335-348 (2005).
142. Kurose, K. et al. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nature Genet. 32, 355-357 (2002).
143. Fukino, K., Shen, L., Patocs, A., Mutter, G. L. & Eng, C. Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. JAMA 297, 2103-2111 (2007).
144. Hu, M. et al. Distinct epigenetic changes in the stromal cells of breast cancers. Nature Genet. 37, 899-905 (2005).
145. Hill, R., Song, Y., Cardiff, R. D. & Van Dyke, T. Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123, 1001-1011 (2005).
146. Lyons, S. K. Advances in imaging mouse tumour models in vivo. J. Pathol. 205, 194-205 (2005).
147. Olive, K. P. & Tuveson, D. A. The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin. Cancer Res. 12, 5277-5287 (2006).
148. Sharpless, N. E. & Depinho, R. A. The mighty mouse: genetically engineered mouse models in cancer drug development. Nature Rev. Drug Discov. 5, 741-754 (2006).
149. Ji, H. et al. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 9, 485-495 (2006).
150. Politi, K. et al. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to downregulation of the receptors. Genes Dev. 20, 1496-1510 (2006). References 149 and 150 demonstrate that mouse cancer models with relevant mutations respond accordingly to currently available therapies.
151. Lallemand-Breitenbach, V. et al. Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia. J. Exp. Med. 189, 1043-1052 (1999). A seminal publication in which therapeutic intervention in a mouse cancer model led to the successful development of an arsenic trioxide as a treatment for childhood acute promyelocytic leukaemia.
152. Soignet, S. & Maslak, P. Therapy of acute promyelocytic leukemia. Adv. Pharmacol. 51, 35-58 (2004).
153. + cells are islet progenitors and are distinct from duct progenitors. Development 129, 2447-2457 (2002).
154. Kawaguchi, Y. et al. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nature Genet. 32, 128-134 (2002).
155. Obata, J. et al. p48 subunit of mouse PTF1 binds to RBP-Jκ/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos. Genes Cells 6, 345-360 (2001).
156. Bardeesy, N. et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 20, 3130-3146 (2006).
157. Loonstra, A. et al. Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc. Natl Acad. Sci. USA 98, 9209-9214 (2001).
158. Pfeifer, A., Brandon, E. P., Kootstra, N., Gage, F. H. & Verma, I. M. Delivery of the Cre recombinase by a self-deleting lentiviral vector: efficient gene targeting in vivo. Proc. Natl Acad. Sci. USA 98, 11450-11455 (2001).
159. Schmidt, E. E., Taylor, D. S., Prigge, J. R., Barnett, S. & Capecchi, M. R. Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc. Natl Acad. Sci. USA 97, 13702-13707 (2000).
160. Raymond, C. S. & Soriano, P. High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells. PLoS ONE 2, e162 (2007).
161. Rodriguez, C. I. et al. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nature Genet. 25, 139-140 (2000).
162. Ehrhardt, A., Xu, H., Huang, Z., Engler, J. A. & Kay, M. A. A direct comparison of two nonviral gene therapy vectors for somatic integration: in vivo evaluation of the bacteriophage integrase phiC31 and the Sleeping Beauty transposase. Mol. Ther. 11, 695-706 (2005).
163. Safran, M. et al. Mouse reporter strain for noninvasive bioluminescent imaging of cells that have undergone Cre-mediated recombination. Mol. Imaging 2, 297-302 (2003).
164. Uhrbom, L., Nerio, E. & Holland, E. C. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nature Med. 10, 1257-1260 (2004).
165. Safran, M. et al. Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. Proc. Natl Acad. Sci. USA 103, 105-110 (2006).
166. Carlsen, H., Moskaug, J. O., Fromm, S. H. & Blomhoff, R. In vivo imaging of NF-κB activity. J. Immunol. 168, 1441-1446 (2002).
167. Meuwissen, R. et al. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4, 181-189 (2003).
168. Sansom, O. J. et al. Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc. Natl Acad. Sci. USA 103, 14122-14127 (2006).
169. Edelmann, W. et al. Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 91, 467-477 (1997).
170. Jonkers, J. et al. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nature Genet. 29, 418-425 (2001).
171. Derksen, P. W. et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10, 437-449 (2006).
172. Aguirre, A. J. et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 17, 3112-3126 (2003).
173. Hingorani, S. R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469-483 (2005).
174. Wang, S. et al. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209-221 (2003).
175. Kim, M. J. et al. Cooperativity of Nkx3. 1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc. Natl Acad. Sci. USA 99, 2884-2889 (2002).
176. Zhou, Z. et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66, 7889-7898 (2006).
177. Colnot, S. et al. Liver-targeted disruption of Apc in mice activates β-catenin signaling and leads to hepatocellular carcinomas. Proc. Natl Acad. Sci. USA 101, 17216-17221 (2004).
178. Zender, L. et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125, 1253-1267 (2006).
179. Santoni-Rugiu, E., Nagy, P., Jensen, M. R., Factor, V. M. & Thorgeirsson, S. S. Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-α. Am. J. Pathol. 149, 407-428 (1996).
180. Dinulescu, D. M. et al. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nature Med. 11, 63-70 (2005).
181. Wu, R. et al. Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways. Cancer Cell 11, 321-333 (2007).
182. Teng, Y. et al. Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse. Cancer Res. 66, 6972-6981 (2006).
183. Opitz, O. G. et al. A mouse model of human oral-esophageal cancer. J. Clin. Invest. 110, 761-769 (2002).
184. Mo, L. et al. Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis. J. Clin. Invest. 117, 314-325 (2007).
185. Sansom, O. J., Griffiths, D. F., Reed, K. R., Winton, D. J. & Clarke, A. R. Apc deficiency predisposes to renal carcinoma in the mouse. Oncogene 24, 8205-8210 (2005).
186. Xiao, A. et al. Somatic induction of Pten loss in a preclinical astrocytoma model reveals major roles in disease progression and avenues for target discovery and validation. Cancer Res. 65, 5172-5180 (2005).
187. Shih, A. H. et al. Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis. Cancer Res. 64, 4783-4789 (2004).
188. Oshima, H. et al. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology 131, 1086-1095 (2006).
189. Andressoo, J. O. et al. An Xpd mouse model for the combined
190. Haramis, A. P. et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303, 1684-1686 (2004).
191. Su, L. K. et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256, 668-670 (1992).
192. Schulze-Garg, C., Lohler, J., Gocht, A. & Deppert, W. A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland. Oncogene 19, 1028-1037 (2000).
193. Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4, 437-450 (2003).
194. Kelavkar, U. P., Parwani, A. V., Shappell, S. B. & Martin, W. D. Conditional expression of human 15-lipoxygenase-1 in mouse prostate induces prostatic intraepithelial neoplasia: the FLiMP mouse model. Neoplasia 8, 510-522 (2006).
195. Abdulkadir, S. A. et al. Conditional loss of Nkx3. 1 in adult mice induces prostatic intraepithelial neoplasia. Mol. Cell Biol. 22, 1495-1503 (2002).
196. Conner, E. A. et al. Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene 19, 5054-5062 (2000).
197. Rankin, E. B., Tomaszewski, J. E. & Haase, V. H. Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res. 66, 2576-2583 (2006).
198. Reilly, K. M., Loisel, D. A., Bronson, R. T., McLaughlin, M. E. & Jacks, T. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nature Genet. 26, 109-113 (2000).
199. Silberg, D. G. et al. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology 122, 689-696 (2002).
200. Pelengaris, S., Littlewood, T., Khan, M., Elia, G. & Evan, G. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol. Cell 3, 565-577 (1999).
201. Bhowmick, N. A. et al. TGF-b signalling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303, 848-851 (2004).