Skip to main content
SpringerLink
Log in

Mouse Models of Breast Cancer

  • Protocol
  • First Online:
Mouse Models of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1267))

Abstract

Breast cancer is the most common cause of cancer death in women worldwide. This malignancy is a complex disease, which is defined by an intrinsic heterogeneity on the histopathological and molecular level as well as response to therapy and outcome. In addition to classical histopathological features, breast cancer can be categorized into at least five major subtypes based on comprehensive gene expression profiling: luminal A, luminal B, basal-like, ERBB2-positive, and normal-like breast cancer. Genetically engineered mouse models can serve as tools to study the molecular underpinnings for this disease. Given the genetic complexity that drives the initiation and progression of individual breast cancer subtypes, it is evident that certain models can reflect only particular aspects of this malignancy. In this book chapter, we will primarily focus on advances in modeling breast cancer at defined stages of carcinogenesis using genetically engineered mice. We will discuss the ability as well as shortcomings of these models to faithfully recapitulate the spectrum of human breast cancer subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wagner KU (2004) Models of breast cancer: quo vadis, animal modeling? Breast Cancer Res 6(1):31–38. doi:10.1186/bcr723

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamen-schikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752. doi:10.1038/35021093

    Article  CAS  PubMed  Google Scholar 

  3. Lin WC, Rajbhandari N, Wagner KU (2014) Cancer cell dormancy in novel mouse models for reversible pancreatic cancer: a lingering challenge in the development of targeted therapies. Cancer Res 74(8):2138–2143. doi:10.1158/0008-5472.CAN-13-3437, 0008-5472.CAN-13-3437 [pii]

    Article  CAS  PubMed  Google Scholar 

  4. Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170(3):793–804

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Utama FE, LeBaron MJ, Neilson LM, Sultan AS, Parlow AF, Wagner KU, Rui H (2006) Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice. J Endocrinol 188(3):589–601. doi:10.1677/joe.1.06560, 188/3/589 [pii]

    Article  CAS  PubMed  Google Scholar 

  6. Ueda O, Tateishi H, Higuchi Y, Fujii E, Kato A, Kawase Y, Wada NA, Tachibe T, Kakefuda M, Goto C, Kawaharada M, Shimaoka S, Hattori K, Jishage K (2013) Novel genetically-humanized mouse model established to evaluate efficacy of therapeutic agents to human interleukin-6 receptor. Sci Rep 3:1196. doi:10.1038/srep01196

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA (2014) Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol 32(4):364–372. doi:10.1038/nbt.2858, nbt.2858 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Stewart TA, Pattengale PK, Leder P (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38(3):627–637

    Article  CAS  PubMed  Google Scholar 

  9. Hennighausen L (2000) Mouse models for breast cancer. Breast Cancer Res 2(1):2–7. doi:10.1186/bcr20

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Van Dyke T, Jacks T (2002) Cancer modeling in the modern era: progress and challenges. Cell 108(2):135–144

    Article  PubMed  Google Scholar 

  11. Donehower LA, Harvey M, Vogel H, McArthur MJ, Montgomery CA Jr, Park SH, Thompson T, Ford RJ, Bradley A (1995) Effects of genetic background on tumorigenesis in p53-deficient mice. Mol Carcinog 14(1):16–22

    Article  CAS  PubMed  Google Scholar 

  12. Ludwig T, Chapman DL, Papaioannou VE, Efstratiadis A (1997) Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev 11(10):1226–1241

    Article  CAS  PubMed  Google Scholar 

  13. Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del Barco Barrantes I, Ho A, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak TW (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 8(21):1169–1178

    Article  CAS  PubMed  Google Scholar 

  14. Matulka LA, Wagner KU (2005) Models of breast cancer. Drug Discov Today Dis Models 2:1–6

    Article  CAS  Google Scholar 

  15. Bittner JJ (1936) Some possible effects of nursing on the mammary gland tumor incidence in mice. Science 84(2172):162. doi:10.1126/science.84.2172.162, 84/2172/162 [pii]

    Article  CAS  PubMed  Google Scholar 

  16. Ross SR (2010) Mouse mammary tumor virus molecular biology and oncogenesis. Viruses 2(9):2000–2012. doi:10.3390/v2092000, viruses-02-02000 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Wagner KU, McAllister K, Ward T, Davis B, Wiseman R, Hennighausen L (2001) Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Res 10(6):545–553

    Article  CAS  PubMed  Google Scholar 

  18. Kordon EC, Smith GH (1998) An entire functional mammary gland may comprise the progeny from a single cell. Development 125(10):1921–1930

    CAS  PubMed  Google Scholar 

  19. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P (1987) Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49(4):465–475

    Article  CAS  PubMed  Google Scholar 

  20. Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE (1988) Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55(4):619–625

    Article  CAS  PubMed  Google Scholar 

  21. Guy CT, Cardiff RD, Muller WJ (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 12(3):954–961

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci U S A 89(22):10578–10582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P (1988) Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54(1):105–115. doi:10.1016/0092-8674(88)90184-5

    Article  CAS  PubMed  Google Scholar 

  24. 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(4):463–472

    Article  CAS  PubMed  Google Scholar 

  25. Wagner KU, Wall RJ, St-Onge L, Gruss P, Wynshaw-Boris A, Garrett L, Li M, Furth PA, Hennighausen L (1997) Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res 25(21):4323–4330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Andrechek ER, Hardy WR, Siegel PM, Rudnicki MA, Cardiff RD, Muller WJ (2000) Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis. Proc Natl Acad Sci U S A 97(7):3444–3449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Sakamoto K, Schmidt JW, Wagner KU (2012) Generation of a novel MMTV-tTA transgenic mouse strain for the targeted expression of genes in the embryonic and postnatal mammary gland. PLoS One 7(8):e43778. doi:10.1371/journal.pone.0043778, PONE-D-12-16928 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Medina D (2000) Mouse models for mammary cancer. In: Ip M, Asch B (eds) Methods in mammary gland biology and breast cancer research. Springer, New York, pp 3–17

    Chapter  Google Scholar 

  29. Rowse GJ, Ritland SR, Gendler SJ (1998) Genetic modulation of neu proto-oncogene-induced mammary tumorigenesis. Cancer Res 58(12):2675–2679

    CAS  PubMed  Google Scholar 

  30. Davie S, Maglione J, Manner C, Young D, Cardiff R, MacLeod C, Ellies L (2007) Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res 16(2):193–201

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Yu Q, Geng Y, Sicinski P (2001) Specific protection against breast cancers by cyclin D1 ablation. Nature 411(6841):1017–1021. doi:10.1038/35082500

    Article  CAS  PubMed  Google Scholar 

  32. Zhang Q, Sakamoto K, Liu C, Triplett AA, Lin WC, Rui H, Wagner KU (2011) Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. Cancer Res 71(24):7513–7524

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Sandgren EP, Schroeder JA, Qui TH, Palmiter RD, Brinster RL, Lee DC (1995) Inhibition of mammary gland involution is associated with transforming growth factor alpha but not c-myc-induced tumorigenesis in transgenic mice. Cancer Res 55(17):3915–3927

    CAS  PubMed  Google Scholar 

  34. Eilon T, Groner B, Barash I (2007) Tumors caused by overexpression and forced activation of Stat5 in mammary epithelial cells of transgenic mice are parity-dependent and developed in aged, postestropausal females. Int J Cancer 121(9):1892–1902

    Article  CAS  PubMed  Google Scholar 

  35. Maroulakou IG, Anver M, Garrett L, Green JE (1994) Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci U S A 91(23):11236–11240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Green JE, Shibata MA, Yoshidome K, Liu ML, Jorcyk C, Anver MR, Wigginton J, Wiltrout R, Shibata E, Kaczmarczyk S, Wang W, Liu ZY, Calvo A, Couldrey C (2000) The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma. Oncogene 19(8):1020–1027. doi:10.1038/sj.onc.1203280

    Article  CAS  PubMed  Google Scholar 

  37. Yoshidome K, Shibata MA, Couldrey C, Korach KS, Green JE (2000) Estrogen promotes mammary tumor development in C3(1)/SV40 large T-antigen transgenic mice: paradoxical loss of estrogen receptoralpha expression during tumor progression. Cancer Res 60(24):6901–6910

    CAS  PubMed  Google Scholar 

  38. Stoesz SP, Gould MN (1995) Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene 11(11):2233–2241

    CAS  PubMed  Google Scholar 

  39. Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP, Schuler LA (2003) Prolactin induces ERalpha-positive and ERalpha-negative mammary cancer in transgenic mice. Oncogene 22(30):4664–4674

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Rose-Hellekant TA, Schroeder MD, Brockman JL, Zhdankin O, Bolstad R, Chen KS, Gould MN, Schuler LA, Sandgren EP (2007) Estrogen receptor-positive mammary tumorigenesis in TGFalpha transgenic mice progresses with progesterone receptor loss. Oncogene 26(36):5238–5246. doi:10.1038/sj.onc.1210340, 1210340 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268(5218):1766–1769

    Article  CAS  PubMed  Google Scholar 

  42. Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A 89(12):5547–5551

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Furth PA, St OL, Boger H, Gruss P, Gossen M, Kistner A, Bujard H, Hennighausen L (1994) Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci U S A 91(20):9302–9306

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Ewald D, Li M, Efrat S, Auer G, Wall RJ, Furth PA, Hennighausen L (1996) Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science 273(5280):1384–1386

    Article  CAS  PubMed  Google Scholar 

  45. 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(3):283–292

    Article  CAS  PubMed  Google Scholar 

  46. Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, Innocent N, Cardiff RD, Schnall MD, Chodosh LA (2002) Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2(6):451–461

    Article  CAS  PubMed  Google Scholar 

  47. 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(6):577–586

    Article  CAS  PubMed  Google Scholar 

  48. 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(4):488–501

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Creamer BA, Triplett AA, Wagner KU (2009) Longitudinal analysis of mammogenesis using a novel tetracycline-inducible mouse model and in vivo imaging. Genesis 47(4):234–245. doi:10.1002/dvg.20480

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. 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(12):2957–2970

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Schmidt JW, Wehde BL, Sakamoto K, Triplett AA, Anderson SM, Tsichlis PN, Leone G, Wagner KU (2014) Stat5 regulates the phosphatidylinositol 3-kinase/Akt1 pathway during mammary gland development and tumorigenesis. Mol Cell Biol 34(7):1363–1377

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Wang H, Karikomi M, Naidu S, Rajmohan R, Caserta E, Chen HZ, Rawahneh M, Moffitt J, Stephens JA, Fernandez SA, Weinstein M, Wang D, Sadee W, La Perle K, Stromberg P, Rosol TJ, Eng C, Ostrowski MC, Leone G (2010) Allele-specific tumor spectrum in Pten knockin mice. Proc Natl Acad Sci U S A 107(11):5142–5147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Jerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, Butel JS, Medina D (2000) A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene 19(8):1052–1058. doi:10.1038/sj.onc.1203270

    Article  CAS  PubMed  Google Scholar 

  54. Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol 6(9):715–725. doi:10.1038/nrm1714

    Article  CAS  PubMed  Google Scholar 

  55. Kuperwasser C, Hurlbut GD, Kittrell FS, Dickinson ES, Laucirica R, Medina D, Naber SP, Jerry DJ (2000) Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice: a model for Li-Fraumeni syndrome. Am J Pathol 157(6):2151–2159

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Chan S, Vermi W, Luo J, Lucini L, Rickert C, Fowler A, Lonardi S, Arthur C, Young L, Levy D, Welch M, Cardiff R, Schreiber R (2012) STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas. Breast Cancer Res 14(1):R16. doi:10.1186/bcr3100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Schneckenleithner C, Bago-Horvath Z, Dolznig H, Neugebauer N, Kollmann K, Kolbe T, Decker T, Kerjaschki D, Wagner KU, Muller M, Stoiber D, Sexl V (2011) Putting the brakes on mammary tumorigenesis: loss of STAT1 predisposes to intraepithelial neoplasias. Oncotarget 2(12):1043–1054, 371 [pii]

    PubMed Central  PubMed  Google Scholar 

  58. Hakem R, de la Pompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, Firpo E, Hui CC, Roberts J, Rossant J, Mak TW (1996) The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 85(7):1009–1023

    Article  CAS  PubMed  Google Scholar 

  59. Liu CY, Flesken-Nikitin A, Li S, Zeng Y, Lee WH (1996) Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. Genes Dev 10(14):1835–1843

    Article  CAS  PubMed  Google Scholar 

  60. Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, Bradley A (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386(6627):804–810. doi:10.1038/386804a0

    Article  CAS  PubMed  Google Scholar 

  61. Suzuki A, de la Pompa JL, Hakem R, Elia A, Yoshida R, Mo R, Nishina H, Chuang T, Wakeham A, Itie A, Koo W, Billia P, Ho A, Fukumoto M, Hui CC, Mak TW (1997) Brca2 is required for embryonic cellular proliferation in the mouse. Genes Dev 11(10):1242–1252

    Article  CAS  PubMed  Google Scholar 

  62. Di CA, Pesce B, Cordon-Cardo C, Pandolfi PP (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet 19(4):348–355. doi:10.1038/1235

    Article  Google Scholar 

  63. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K (1994) Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265(5168):103–106

    Article  CAS  PubMed  Google Scholar 

  64. Kuhn R, Torres RM (2002) Cre/loxP recombination system and gene targeting. Methods Mol Biol 180:175–204. doi:10.1385/1-59259-178-7:175, 1-59259-178-7-175 [pii]

    CAS  PubMed  Google Scholar 

  65. Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A, Deng CX (1999) Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet 22(1):37–43. doi:10.1038/8743

    Article  CAS  PubMed  Google Scholar 

  66. Backman SA, Ghazarian D, So K, Sanchez O, Wagner KU, Hennighausen L, Suzuki A, Tsao MS, Chapman WB, Stambolic V, Mak TW (2004) Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten. Proc Natl Acad Sci U S A 101(6):1725–1730. doi:10.1073/pnas.0308217100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Cheung AMY, Elia A, Tsao MS, Done S, Wagner KU, Hennighausen L, Hakem R, Mak TW (2004) Brca2 deficiency does not impair mammary epithelium development but promotes mammary adenocarcinoma formation in p53+/GêÆ mutant mice. Cancer Res 64(6):1959–1965

    Article  CAS  PubMed  Google Scholar 

  68. Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner KU, Wu DC, Lane TF, Liu X, Hennighausen L, Wu H (2002) Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129(17):4159–4170

    CAS  PubMed  Google Scholar 

  69. UrsiniGÇÉSiegel J, Hardy WR, Zuo D, Lam SH, Sanguin Gendreau V, Cardiff RD, Pawson T, Muller WJ (2008) ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO J 27(6):910–920. doi:10.1038/emboj.2008.22

    Article  CAS  Google Scholar 

  70. Selbert S, Bentley DJ, Melton DW, Rannie D, Lourenco P, Watson CJ, Clarke AR (1998) Efficient BLG-Cre mediated gene deletion in the mammary gland. Transgenic Res 7(5):387–396

    Article  CAS  PubMed  Google Scholar 

  71. Ludwig T, Fisher P, Murty V, Efstratiadis A (2001) Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice. Oncogene 20(30):3937–3948. doi:10.1038/sj.onc.1204512

    Article  CAS  PubMed  Google Scholar 

  72. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A (2001) Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 29(4):418–425. doi:10.1038/ng747, ng747 [pii]

    Article  CAS  PubMed  Google Scholar 

  73. Smart C, Clarke C, Brooks K, Raghavendra A, Brewster B, French J, Hetherington R, Fleming J, Rothnagel J, Wainwright B, Lakhani S, Brown M (2008) Targeted disruption of Brca1 in restricted compartments of the mouse mammary epithelia. Breast Cancer Res Treat 112(2):237–241

    Article  PubMed  Google Scholar 

  74. Berton TR, Matsumoto T, Page A, Conti CJ, Deng CX, Jorcano JL, Johnson DG (2003) Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues. Oncogene 22(35):5415–5426. doi:10.1038/sj.onc.1206825, 1206825 [pii]

    Article  CAS  PubMed  Google Scholar 

  75. Triplett AA, Montagna C, Wagner KU (2008) A mammary-specific, long-range deletion on mouse chromosome 11 accelerates Brca1-associated mammary tumorigenesis. Neoplasia 10(12):1325–1334

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE, Lindeman GJ (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15(8):907–913

    Article  CAS  PubMed  Google Scholar 

  77. Honrado E, Benitez J, Palacios J (2006) Histopathology of BRCA1- and BRCA2-associated breast cancer. Crit Rev Oncol Hematol 59(1):27–39. doi:10.1016/j.critrevonc.2006.01.006

    Article  PubMed  Google Scholar 

  78. Wagner KU, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, Smith GH (2002) An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development 129(6):1377–1386

    CAS  PubMed  Google Scholar 

  79. Matulka LA, Triplett AA, Wagner KU (2007) Parity-induced mammary epithelial cells are multipotent and express cell surface markers associated with stem cells. Dev Biol 303(1):29–44

    Article  CAS  PubMed  Google Scholar 

  80. Henry MD, Triplett AA, Oh KB, Smith GH, Wagner KU (2004) Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene 23(41):6980–6985

    Article  CAS  PubMed  Google Scholar 

  81. Klinakis A, Szabolcs M, Chen G, Xuan S, Hibshoosh H, Efstratiadis A (2009) Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc Natl Acad Sci U S A 106(7):2359–2364

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Schade B, Lesurf R, Sanguin-Gendreau V, Bui T, Deblois G, O’Toole SA, Millar EK, Zardawi SJ, Lopez-Knowles E, Sutherland RL, Giguere V, Kahn M, Hallett M, Muller WJ (2013) beta-Catenin signaling is a critical event in ErbB2-mediated mammary tumor progression. Cancer Res 73(14):4474–4487. doi:10.1158/0008-5472.CAN-12-3925

    Article  CAS  PubMed  Google Scholar 

  83. Sakamoto K, Lin WC, Triplett AA, Wagner KU (2009) Targeting janus kinase 2 in Her2/neu-expressing mammary cancer: implications for cancer prevention and therapy. Cancer Res 69(16):6642–6650

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Sakamoto K, Triplett AA, Schuler LA, Wagner KU (2010) Janus kinase 2 is required for the initiation but not maintenance of prolactin-induced mammary cancer. Oncogene 29(39):5359–5369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Cardiff RD, Anver MR, Gusterson BA, Hennighausen L, Jensen RA, Merino MJ, Rehm S, Russo J, Tavassoli FA, Wakefield LM, Ward JM, Green JE (2000) The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene 19(8):968–988

    Article  CAS  PubMed  Google Scholar 

  86. Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong JL, Naidu S, Wei G, Sharma SM, Stephens JA, Fernandez SA, Gurcan MN, Weinstein MB, Barsky SH, Yee L, Rosol TJ, Stromberg PC, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC, Leone G (2009) Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 461(7267):1084–1091. doi:10.1038/nature08486, nature08486 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Herschkowitz J, Simin K, Weigman V, Mikaelian I, Usary J, Hu Z, Rasmussen K, Jones L, Assefnia S, Chandrasekharan S, Backlund M, Yin Y, Khramtsov A, Bastein R, Quackenbush J, Glazer R, Brown P, Green J, Kopelovich L, Furth P, Palazzo J, Olopade O, Bernard P, Churchill G, Van Dyke T, Perou C (2007) Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8(5):R76. doi:10.1186/gb-2007-8-5-r76

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  88. Pfefferle A, Herschkowitz J, Usary J, Harrell J, Spike B, Adams J, Torres-Arzayus M, Brown M, Egan S, Wahl G, Rosen J, Perou C (2013) Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts. Genome Biol 14(11):R125. doi:10.1186/gb-2013-14-11-r125

    Article  PubMed Central  PubMed  Google Scholar 

  89. Fantozzi A, Christofori G (2006) Mouse models of breast cancer metastasis. Breast Cancer Res 8(4):212. doi:10.1186/bcr1530

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Aslakson CJ, Miller FR (1992) Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res 52(6):1399–1405

    CAS  PubMed  Google Scholar 

  91. Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64(19):7022–7029

    Article  CAS  PubMed  Google Scholar 

  92. Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193(6):727–740

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Ranger JJ, Levy DE, Shahalizadeh S, Hallett M, Muller WJ (2009) Identification of a Stat3-dependent transcription regulatory network involved in metastatic progression. Cancer Res 69(17):6823–6830

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Wakefield A, Soukupova J, Montagne A, Ranger J, French R, Muller WJ, Clarkson RWE (2013) Bcl3 selectively promotes metastasis of ERBB2-driven mammary tumors. Cancer Res 73(2):745–755

    Article  CAS  PubMed  Google Scholar 

  95. Adams JR, Xu K, Liu JC, Agamez NMR, Loch AJ, Wong RG, Wang W, Wright KL, Lane TF, Zacksenhaus E, Egan SE (2011) Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation. Cancer Res 71(7):2706–2717

    Article  CAS  PubMed  Google Scholar 

  96. Meyer DS, Brinkhaus H, Müller U, Müller M, Cardiff RD, Bentires-Alj M (2011) Luminal expression of PIK3CA mutant H1047R in the mammary gland induces heterogeneous tumors. Cancer Res 71(13):4344–4351

    Article  CAS  PubMed  Google Scholar 

  97. Tikoo A, Roh V, Montgomery KG, Ivetac I, Waring P, Pelzer R, Hare L, Shackleton M, Humbert P, Phillips WA (2012) Physiological levels of Pik3ca(H1047R) mutation in the mouse mammary gland results in ductal hyperplasia and formation of ERalpha-positive tumors. PLoS One 7(5):e36924. doi:10.1371/journal.pone.0036924

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Yuan W, Stawiski E, Janakiraman V, Chan E, Durinck S, Edgar KA, Kljavin NM, Rivers CS, Gnad F, Roose-Girma M, Haverty PM, Fedorowicz G, Heldens S, Soriano RH, Zhang Z, Wallin JJ, Johnson L, Merchant M, Modrusan Z, Stern HM, Seshagiri S (2013) Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations. Oncogene 32(3):318–326. doi:10.1038/onc.2012.53, onc201253 [pii]

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Blanco-Aparicio C, Perez-Gallego L, Pequeno B, Leal JF, Renner O, Carnero A (2007) Mice expressing myrAKT1 in the mammary gland develop carcinogen-induced ER-positive mammary tumors that mimic human breast cancer. Carcinogenesis 28(3):584–594. doi:10.1093/carcin/bgl190

    Article  CAS  PubMed  Google Scholar 

  100. Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner KU, Diehl JA (2008) Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene 27(9):1231–1242

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. McCarthy A, Savage K, Gabriel A, Naceur C, Reis-Filho JS, Ashworth A (2007) A mouse model of basal-like breast carcinoma with metaplastic elements. J Pathol 211(4):389–398

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE, 68198-5950, USA

    Kazuhito Sakamoto, Jeffrey W. Schmidt & Kay-Uwe Wagner

  2. Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE, 68198-5950, USA

    Kazuhito Sakamoto, Jeffrey W. Schmidt & Kay-Uwe Wagner

Authors
  1. Kazuhito Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey W. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kay-Uwe Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kazuhito Sakamoto or Kay-Uwe Wagner .

Editor information

Editors and Affiliations

  1. Medical University Vienna (MUV) Institute for Cancer Research, Vienna, Austria

    Robert Eferl

  2. Research (LBI-CR), Medical University Vienna (MUV), Center of Physiology and Pharmacology & Ludwig Boltzmann Institute for Cancer, Vienna, Austria

    Emilio Casanova

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Sakamoto, K., Schmidt, J.W., Wagner, KU. (2015). Mouse Models of Breast Cancer. In: Eferl, R., Casanova, E. (eds) Mouse Models of Cancer. Methods in Molecular Biology, vol 1267. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2297-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2297-0_3

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2296-3

  • Online ISBN: 978-1-4939-2297-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation