Mouse models of cancer.

Genetically engineered mouse models have significantly contributed to our understanding of cancer biology. They have proven to be useful in validating gene functions, identifying novel cancer genes and tumor biomarkers, gaining insight into the molecular and cellular mechanisms underlying tumor initiation and multistage processes of tumorigenesis, and providing better clinical models in which to test novel therapeutic strategies. However, mice still have significant limitations in modeling human cancer, including species-specific differences and inaccurate recapitulation of de novo human tumor development. Future challenges in mouse modeling include the generation of clinically relevant mouse models that recapitulate the molecular, cellular, and genomic events of human cancers and clinical response as well as the development of technologies that allow for efficient in vivo imaging and high-throughput screening in mice.

[1]  W. Murray A NOTE ON OVARIAN SECRETION AND CANCER. , 1928, Science.

[2]  A. Tannenbaum,et al.  The influence of the degree of caloric restriction on the formation of skin tumors and hepatomas in mice. , 1949, Cancer research.

[3]  V. Jordan Effects of tamoxifen in relation to breast cancer. , 1977, British medical journal.

[4]  P. Hunsicker,et al.  Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[5]  P. Leder,et al.  Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes , 1984, Cell.

[6]  R. Palmiter,et al.  Transgenic mice harboring SV40 t-antigen genes develop characteristic brain tumors , 1984, Cell.

[7]  M. Zijlstra,et al.  Involvement of c‐myc in MuLV‐induced T cell lymphomas in mice: frequency and mechanisms of activation. , 1984, The EMBO journal.

[8]  D. Hanahan,et al.  Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. , 1985, Nature.

[9]  A. Berns,et al.  Proviral activation of the putative oncogene Pim‐1 in MuLV induced T‐cell lymphomas. , 1985, The EMBO journal.

[10]  R. Palmiter,et al.  The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice , 1985, Nature.

[11]  A. Knudson,et al.  Genetics of human cancer. , 1986, Annual review of genetics.

[12]  R. Hoess,et al.  The role of the loxP spacer region in P1 site-specific recombination. , 1986, Nucleic acids research.

[13]  M. Capecchi,et al.  Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells , 1987, Cell.

[14]  N. Copeland,et al.  Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors , 1988, Molecular and cellular biology.

[15]  A. Berns,et al.  Predisposition to lymphomagenesis in pim-1 transgenic mice: Cooperation with c-myc and N-myc in murine leukemia virus-induced tumors , 1989, Cell.

[16]  L. Strong,et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. , 1990, Science.

[17]  H. Pitot,et al.  A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. , 1990, Science.

[18]  Philippe Soriano,et al.  Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. , 1991, Genes & development.

[19]  A. Berns,et al.  Carcinogen-induced lymphomagenesis in pim-1 transgenic mice: dose dependence and involvement of myc and ras. , 1991, Cancer research.

[20]  Anton Berns,et al.  Identification of cooperating oncogenes in Eμ-myc transgenic mice by provirus tagging , 1991, Cell.

[21]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[22]  R. Weinberg,et al.  Effects of an Rb mutation in the mouse , 1992, Nature.

[23]  K. Kinzler,et al.  Erratum: Multiple Intestinal Neoplasia Caused By a Mutation in the Murine Homolog of the APC Gene , 1992, Science.

[24]  P. Demant Genetic resolution of susceptibility to cancer--new perspectives. , 1992, Seminars in cancer biology.

[25]  R. Weinberg,et al.  Tumor spectrum analysis in p53-mutant mice , 1994, Current Biology.

[26]  B. Koller,et al.  Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities , 1996, Nature Genetics.

[27]  J. Rossant,et al.  The Tumor Suppressor Gene Brca1 Is Required for Embryonic Cellular Proliferation in the Mouse , 1996, Cell.

[28]  G M Edelman,et al.  Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  W F Bodmer,et al.  Dietary fat influences on polyp phenotype in multiple intestinal neoplasia mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[30]  James M. Roberts,et al.  The murine gene p27Kip1 is haplo-insufficient for tumour suppression , 1998, Nature.

[31]  R. Xavier,et al.  Tumor Induction of VEGF Promoter Activity in Stromal Cells , 1998, Cell.

[32]  P. Pharoah,et al.  Increased frequency of TP53 mutations in BRCA1 and BRCA2 ovarian tumours , 1999, Genes, chromosomes & cancer.

[33]  Thomas Ried,et al.  Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation , 1999, Nature Genetics.

[34]  T. van Dyke,et al.  Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice. , 1999, Cancer research.

[35]  Philippe Soriano Generalized lacZ expression with the ROSA26 Cre reporter strain , 1999, Nature Genetics.

[36]  G. Evan,et al.  Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. , 1999, Molecular cell.

[37]  S. Kogan,et al.  Retinoic Acid and Arsenic Synergize to Eradicate Leukemic Cells in a Mouse Model of Acute Promyelocytic Leukemia , 1999, The Journal of experimental medicine.

[38]  L. Chin,et al.  Essential role for oncogenic Ras in tumour maintenance , 1999, Nature.

[39]  D. Hanahan,et al.  Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. , 1999, Science.

[40]  M. Scott,et al.  Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice , 1999, Nature Medicine.

[41]  P. Pandolfi,et al.  Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[42]  E. Sandgren,et al.  Transforming growth factor alpha- and c-myc-induced mammary carcinogenesis in transgenic mice , 2000, Oncogene.

[43]  R. Plasterk,et al.  Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. , 2000, Journal of molecular biology.

[44]  Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor. , 2000, Cancer research.

[45]  Caiying Guo,et al.  Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon cre‐mediated excision , 2000, Genesis.

[46]  G. Merlino,et al.  Accelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth factor/scatter factor transgenic mice. , 2000, Cancer research.

[47]  A. Trumpp,et al.  Inducible chromosomal translocation of AML1 and ETO genes through Cre/loxP‐mediated recombination in the mouse , 2000, EMBO reports.

[48]  Curtis C. Harris,et al.  Genetic interactions between tumor suppressors Brca1 and p53 in apoptosis, cell cycle and tumorigenesis , 2001, Nature Genetics.

[49]  A. Bradley,et al.  Engineering chromosomal rearrangements in mice , 2001, Nature Reviews Genetics.

[50]  A. Balmain,et al.  Building 'validated' mouse models of human cancer. , 2001, Current opinion in cell biology.

[51]  A. Berns,et al.  Mouse models for sporadic cancer. , 2001, Experimental cell research.

[52]  T. Jacks,et al.  Somatic activation of the K-ras oncogene causes early onset lung cancer in mice , 2001, Nature.

[53]  T. Jacks,et al.  Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. , 2001, Genes & development.

[54]  H. Varmus,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. , 2001, Genes & development.

[55]  H. Ruley,et al.  Epigenetic regulation of gene structure and function with a cell-permeable Cre recombinase , 2001, Nature Biotechnology.

[56]  A. Buchmann,et al.  Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of β-catenin-mutated mouse liver tumors , 2001, Oncogene.

[57]  F. Gage,et al.  Delivery of the Cre recombinase by a self-deleting lentiviral vector: Efficient gene targeting in vivo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[58]  P. Duray,et al.  Neonatal sunburn and melanoma in mice , 2001, Nature.

[59]  T. Jacks,et al.  Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Adrian L. Harris,et al.  Hypoxia — a key regulatory factor in tumour growth , 2002, Nature Reviews Cancer.

[61]  David Baltimore,et al.  Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors , 2002, Science.

[62]  A. West,et al.  Insulators: many functions, many mechanisms. , 2002, Genes & development.

[63]  Jos Jonkers,et al.  Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. , 2002, Cancer research.

[64]  H. Varmus,et al.  Induction of ovarian cancer by defined multiple genetic changes in a mouse model system. , 2002, Cancer cell.

[65]  Cestmir Vlcek,et al.  Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers , 2002, Nature Genetics.

[66]  Susumu Minamisawa,et al.  ErbB2 is essential in the prevention of dilated cardiomyopathy , 2002, Nature Medicine.

[67]  P. Demant,et al.  Cancer susceptibility in the mouse: genetics, biology and implications for human cancer , 2003, Nature Reviews Genetics.

[68]  D. Largaespada,et al.  Gene transfer into genomes of human cells by the sleeping beauty transposon system. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[69]  T. Pawson,et al.  Transgenic RNA interference in ES cell–derived embryos recapitulates a genetic null phenotype , 2003, Nature Biotechnology.

[70]  Robert A. Weinberg,et al.  Comparative Biology of Mouse versus Human Cells: Modelling Human Cancer in Mice O P I N I O N , 2022 .

[71]  N. Greenberg,et al.  SU5416 selectively impairs angiogenesis to induce prostate cancer-specific apoptosis. , 2003, Molecular cancer therapeutics.

[72]  E. Petricoin,et al.  Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. , 2003, Cancer cell.

[73]  C. Conti,et al.  Advances in molecular carcinogenesis: current and future use of mouse models to screen and validate molecularly targeted anticancer drugs , 2004, Molecular carcinogenesis.

[74]  C. Perou,et al.  MYC Is Amplified in BRCA1-Associated Breast Cancers , 2004, Clinical Cancer Research.

[75]  E. Holland,et al.  Somatic Cell Gene Transfer , 2004 .

[76]  G. Rao,et al.  Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice , 2004, Oncogene.

[77]  Carl-Fredrik Tiger,et al.  Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[78]  P. Pandolfi,et al.  Germline Modification Strategies , 2004 .

[79]  P. Sharp,et al.  Cre-lox-regulated conditional RNA interference from transgenes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[80]  Oriol Casanovas,et al.  Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. , 2005, Cancer cell.

[81]  Corey M. Carlson,et al.  Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse , 2005, Nature.

[82]  S. Lyons Advances in imaging mouse tumour models in vivo , 2005, The Journal of pathology.

[83]  A. Berns,et al.  Retroviral insertional mutagenesis: past, present and future , 2005, Oncogene.

[84]  D. Largaespada,et al.  Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system , 2005, Nature.

[85]  T. Jacks,et al.  Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer , 2005, Nature Medicine.

[86]  Robert D. Cardiff,et al.  Selective Evolution of Stromal Mesenchyme with p53 Loss in Response to Epithelial Tumorigenesis , 2005, Cell.

[87]  J. Mesirov,et al.  An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis , 2005, Nature Genetics.

[88]  David A Largaespada,et al.  Hopping around the tumor genome: transposons for cancer gene discovery. , 2005, Cancer research.

[89]  Min Han,et al.  Efficient Transposition of the piggyBac (PB) Transposon in Mammalian Cells and Mice , 2005, Cell.

[90]  J. Nadeau,et al.  The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours , 2005, Nature.

[91]  L. Luo,et al.  Mosaic Analysis with Double Markers in Mice , 2005, Cell.

[92]  X. Coumoul,et al.  Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference , 2005, Nucleic acids research.

[93]  P. Pharoah,et al.  Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1 , 2005, Nature Genetics.

[94]  M. Wilkinson,et al.  Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis. , 2006, Genes & development.

[95]  R. DePinho,et al.  Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Takeshi Suzuki,et al.  Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm‐deficient mice , 2006, The EMBO journal.

[97]  Rudolf Jaenisch,et al.  Efficient method to generate single‐copy transgenic mice by site‐specific integration in embryonic stem cells , 2006, Genesis.

[98]  A. Berns,et al.  Cross-Species Oncogenomics in Cancer Gene Identification , 2006, Cell.

[99]  L. Chin,et al.  Comparative Oncogenomics Identifies NEDD9 as a Melanoma Metastasis Gene , 2006, Cell.

[100]  Ronald A. DePinho,et al.  Model organisms: The mighty mouse: genetically engineered mouse models in cancer drug development , 2006, Nature Reviews Drug Discovery.

[101]  M. Wigler,et al.  Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic Approach , 2006, Cell.

[102]  D. Xing,et al.  A mouse model for the molecular characterization of brca1-associated ovarian carcinoma. , 2006, Cancer research.

[103]  G. Evan,et al.  Tumor angiogenesis: cause or consequence of cancer? , 2007, Cancer research.

[104]  A. Bradley,et al.  Generation of an inducible and optimized piggyBac transposon system , 2007, Nucleic acids research.

[105]  L. Luo Fly MARCM and mouse MADM: Genetic methods of labeling and manipulating single neurons , 2007, Brain Research Reviews.

[106]  A. Bradley,et al.  Induced mitotic recombination of p53 in vivo , 2007, Proceedings of the National Academy of Sciences.

[107]  L. Luo,et al.  Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM) , 2007, Proceedings of the National Academy of Sciences.

[108]  P. Polakis The many ways of Wnt in cancer. , 2007, Current opinion in genetics & development.

[109]  Sen Wu,et al.  Toward simpler and faster genome-wide mutagenesis in mice , 2007, Nature Genetics.

[110]  H. Vogel,et al.  CHD5 Is a Tumor Suppressor at Human 1p36 , 2007, Cell.

[111]  G. Lucignani,et al.  Cancer modeling: modern imaging applications in the generation of novel animal model systems to study cancer progression and therapy. , 2007, The international journal of biochemistry & cell biology.

[112]  David A. Tuveson,et al.  Maximizing mouse cancer models , 2007, Nature Reviews Cancer.

[113]  Heidi Zhang,et al.  Integrated pipeline for mass spectrometry-based discovery and confirmation of biomarkers demonstrated in a mouse model of breast cancer. , 2007, Journal of proteome research.

[114]  L. Chin,et al.  Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers , 2007, Nature.

[115]  David Bouchez,et al.  Manipulating the Mouse Embryo , 2007 .

[116]  J. Hughes,et al.  Manipulating the Mouse Genome to Engineer Precise Functional Syntenic Replacements with Human Sequence , 2007, Cell.

[117]  S. Lowe,et al.  Tissue-specific and reversible RNA interference in transgenic mice , 2007, Nature Genetics.

[118]  G. Evan,et al.  Distinct thresholds govern Myc's biological output in vivo. , 2008, Cancer cell.

[119]  S. Hanash,et al.  Mining the plasma proteome for cancer biomarkers , 2008, Nature.

[120]  S. Hayward,et al.  Prostate tumor progression is mediated by a paracrine TGF-β/Wnt3a signaling axis , 2008, Oncogene.

[121]  A. Krasnitz,et al.  DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma. , 2008, Genes & development.

[122]  A. Krasnitz,et al.  An Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer , 2008, Cell.

[123]  Jeffrey S. Han,et al.  Conditional activation of a single‐copy L1 transgene in mice by Cre , 2008, Genesis.

[124]  Michelle A. Anderson,et al.  A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development , 2008, PLoS medicine.

[125]  C. Yeang,et al.  Combinatorial patterns of somatic gene mutations in cancer , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[126]  Robert M. Hoffman,et al.  Imaging cancer dynamics in vivo at the tumor and cellular level with fluorescent proteins , 2008, Clinical & Experimental Metastasis.

[127]  Kazushi Inoue,et al.  MMTV mouse models and the diagnostic values of MMTV-like sequences in human breast cancer , 2009, Expert review of molecular diagnostics.

[128]  Akira Niwa,et al.  Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreERT21 , 2009, The Journal of Immunology.

[129]  Liese C C Pruitt,et al.  Integrated Proteomic Analysis of Human Cancer Cells and Plasma from Tumor Bearing Mice for Ovarian Cancer Biomarker Discovery , 2009, PloS one.

[130]  T. Scheetz,et al.  A modified sleeping beauty transposon system that can be used to model a wide variety of human cancers in mice. , 2009, Cancer research.

[131]  J. Downing,et al.  Mouse models of human AML accurately predict chemotherapy response. , 2009, Genes & development.

[132]  David J. Adams,et al.  Cancer gene discovery in mouse and man , 2009, Biochimica et biophysica acta.

[133]  M. Habiba,et al.  The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse. , 2009, Reproduction.

[134]  Yoichi Gondo,et al.  Next-generation gene targeting in the mouse for functional genomics. , 2009, BMB reports.

[135]  M. Katoh,et al.  Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. , 2009, Current molecular medicine.

[136]  Eyal Gottlieb,et al.  Metabolic transformation in cancer. , 2009, Carcinogenesis.

[137]  Y. Asmann,et al.  A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer , 2009, Science.

[138]  G. Vassiliou,et al.  New approaches for modelling sporadic genetic disease in the mouse , 2009, Disease Models & Mechanisms.

[139]  S. Hanash,et al.  Comprehensive Proteome Analysis of an Apc Mouse Model Uncovers Proteins Associated with Intestinal Tumorigenesis , 2009, Cancer Prevention Research.

[140]  A. Krasnitz,et al.  Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. , 2009, Cancer cell.

[141]  L. Luo,et al.  Uncoupling Dendrite Growth and Patterning: Single-Cell Knockout Analysis of NMDA Receptor 2B , 2009, Neuron.

[142]  Derek Y. Chiang,et al.  A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma , 2009, Nature Biotechnology.

[143]  L. Chin,et al.  Chimeric mouse tumor models reveal differences in pathway activation between ERBB family– and KRAS-dependent lung adenocarcinomas , 2010, Nature Biotechnology.