The Relevance of Mouse Models to Understanding the Development and Progression of Human Breast Cancer



Mouse modeling of human breast cancer has developed tremendously over the past ten years. Human breast cancer is characterized by enormous biological diversity and, collectively, the new models have come much closer to encompassing this diversity. They have provided a deeper understanding of the fundamental events that mediate the initiation, development, and progression of breast cancer, and they offer new opportunities to develop and test strategies to treat and, perhaps, even prevent the disease. This chapter reviews the historical development of mouse models of breast cancer and highlights some of their major strengths, weaknesses, and contributions.


Breast cancer Mouse model 



terminal duct lobular units


columnar cell hyperplasia


hyperplastic enlarged lobular units


atypical ductal hyperplasia


ductal carcinoma in situ


invasive breast cancer


atypical lobular hyperplasia


lobular carcinoma in situ


infiltrating lobular carcinoma


epithelial-mesenchymal transition


  1. 1.
    Allred DC, Wu Y, Mao S, Nagtegaal ID, Lee S, Perou CM, et al. Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clin Cancer Res. 2008;14(2):370–8. doi: 10.1158/1078-0432.CCR-07-1127.PubMedCrossRefGoogle Scholar
  2. 2.
    Wellings RR, Jensen HM. On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst. 1973;50:1111–8.PubMedGoogle Scholar
  3. 3.
    Wellings SR, Jensen HM, Marcum RG. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst. 1975;55(2):231–73.PubMedGoogle Scholar
  4. 4.
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998;90(18):1371–88. doi: 10.1093/jnci/90.18.1371.PubMedCrossRefGoogle Scholar
  5. 5.
    Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene STAR P-2 trial. JAMA. 2006;295(23):2727–41. doi: 10.1001/jama.295.23.joc60074.PubMedCrossRefGoogle Scholar
  6. 6.
    Medina D. Mouse models for mammary cancer. In: Asch BB, Ip MM, editors. Methods in Mammary Gland Biology and Breast Cancer Research. New York: Kluwer Academic Press; 2000. p. 3–17.Google Scholar
  7. 7.
    Deome KB, Faulkin LJ Jr, Bern HA, Blair PB. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959;19(5):515–20.PubMedGoogle Scholar
  8. 8.
    Medina D. Premalignant and malignant mammary lesions induced by MMTV and chemical carcinogens. J Mammary Gland Biol Neoplasia. 2008. doi: 10.1007/s10911-008-9086-4.
  9. 9.
    von Lintig FC, Dreilinger AD, Varki NM, Wallace AM, Casteel DE, Boss GR. Ras activation in human breast cancer. Breast Cancer Res Treat. 2000;62(1):51–62. doi: 10.1023/A:1006491619920.CrossRefGoogle Scholar
  10. 10.
    Borowsky A. Special considerations in mouse models of breast cancer. Breast Dis. 2007;28:29–38.PubMedGoogle Scholar
  11. 11.
    Shen Q, Brown PH. Novel agents for the prevention of breast cancer: targeting transcription factors and signal transduction pathways. J Mammary Gland Biol Neoplasia. 2003;8(1):45–73. doi: 10.1023/A:1025783221557.PubMedCrossRefGoogle Scholar
  12. 12.
    Boxer RB, Jang JW, Sintasath L, Chodosh LA. Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell. 2004;6(6):577–86. doi: 10.1016/j.ccr.2004.10.013.PubMedCrossRefGoogle Scholar
  13. 13.
    Li W, Xiao C, Vonderhaar BK, Deng CX. A role of estrogen/ERalpha signaling in BRCA1-associated tissue-specific tumor formation. Oncogene. 2007;26(51):7204–12. doi: 10.1038/sj.onc.1210527.PubMedCrossRefGoogle Scholar
  14. 14.
    Lin SC, Lee KF, Nikitin AY, Hilsenbeck SG, Cardiff RD, Li A, et al. Somatic mutation of p53 leads to estrogen receptor alpha-positive and -negative mouse mammary tumors with high frequency of metastasis. Cancer Res. 2004;64(10):3525–32. doi: 10.1158/0008-5472.CAN-03-3524.PubMedCrossRefGoogle Scholar
  15. 15.
    Jang JW, Boxer RB, Chodosh LA. Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol Cell Biol. 2006;26(21):8109–21. doi: 10.1128/MCB.00404-06.PubMedCrossRefGoogle Scholar
  16. 16.
    Du Z, Li Y. RCAS-TVA in the mammary gland: an in vivo oncogene screen and a high fidelity model for breast transformation? Cell Cycle. 2007;6(7):823–6.PubMedGoogle Scholar
  17. 17.
    Cardiff RD, Moghanaki D, Jensen RA. Genetically engineered mouse models of mammary intraepithelial neoplasia. J Mammary Gland Biol Neoplasia. 2000;5(4):421–37. doi: 10.1023/A:1009534129331.PubMedCrossRefGoogle Scholar
  18. 18.
    Aidells BD, Daniel CW. Hormone-dependent mammary tumors in strain GR-A mice. I. Alternation between ductal and tumorous phases of growth during serial transplantation. J Natl Cancer Inst. 1974;52(6):1855–63.PubMedGoogle Scholar
  19. 19.
    Aidells BD, Daniel CW. Hormone-dependent mammary tumors in strain GR/A mice. IV. Origin and progression. J Natl Cancer Inst. 1978;60(6):1345–50.PubMedGoogle Scholar
  20. 20.
    Kordon EC, Molinolo AA, Pasqualini CD, Charreau EH, Pazos P, Dran G, et al. Progesterone induction of mammary carcinomas in BALB/c female mice. Correlation between progestin dependence and morphology. Breast Cancer Res Treat. 1993;28(1):29–39. doi: 10.1007/BF00666353.PubMedCrossRefGoogle Scholar
  21. 21.
    Pazos P, Lanari C, Elizalde P, Montecchia F, Charreau EH, Molinolo AA. Promoter effect of medroxyprogesterone acetate (MPA) in N-methyl-N-nitrosourea (MNU) induced mammary tumors in BALB/c mice. Carcinogenesis. 1998;19(3):529–31. doi: 10.1093/carcin/19.3.529.PubMedCrossRefGoogle Scholar
  22. 22.
    Efeyan A, Fabris V, Merani S, Lanari C, Molinolo AA. Establishment of two hormone-responsive mouse mammary carcinoma cell lines derived from a metastatic mammary tumor. Breast Cancer Res Treat. 2004;83(3):233–44. doi: 10.1023/ Scholar
  23. 23.
    Jerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, et al. A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene. 2000;19(8):1052–8. doi: 10.1038/sj.onc.1203270.PubMedCrossRefGoogle Scholar
  24. 24.
    Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, et al. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 2004;119(6):861–72. doi: 10.1016/j.cell.2004.11.006.PubMedCrossRefGoogle Scholar
  25. 25.
    Medina D, Kittrell FS, Hill J, Shepard A, Thordarson G, Brown P. Tamoxifen inhibition of estrogen receptor-alpha-negative mouse mammary tumorigenesis. Cancer Res. 2005;65(8):3493–6.PubMedGoogle Scholar
  26. 26.
    Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science. 2006;314(5804):1467–70. doi: 10.1126/science.1130471.PubMedCrossRefGoogle Scholar
  27. 27.
    Hu Y, Sun H, Drake J, Kittrell F, Abba MC, Deng L, et al. From mice to humans: identification of commonly deregulated genes in mammary cancer via comparative SAGE studies. Cancer Res. 2004;64(21):7748–55. doi: 10.1158/0008-5472.CAN-04-1827.PubMedCrossRefGoogle Scholar
  28. 28.
    Frech MS, Halama ED, Tilli MT, Singh B, Gunther EJ, Chodosh LA, et al. Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Res. 2005;65(3):681–5.PubMedGoogle Scholar
  29. 29.
    Jones LP, Tilli MT, Assefnia S, Torre K, Halama ED, Parrish A, et al. Activation of estrogen signaling pathways collaborates with loss of Brca1 to promote development of ERalpha-negative and ERalpha-positive mammary preneoplasia and cancer. Oncogene. 2008;27(6):794–802. doi: 10.1038/sj.onc.1210674.PubMedCrossRefGoogle Scholar
  30. 30.
    Tilli MT, Frech MS, Steed ME, Hruska KS, Johnson MD, Flaws JA, et al. Introduction of estrogen receptor-alpha into the tTA/TAg conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma. Am J Pathol. 2003;163(5):1713–9.PubMedGoogle Scholar
  31. 31.
    Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006;10(6):529–41. doi: 10.1016/j.ccr.2006.10.009.PubMedCrossRefGoogle Scholar
  32. 32.
    DePinho RA. The age of cancer. Nature. 2000;408(6809):248–54. doi: 10.1038/35041694.PubMedCrossRefGoogle Scholar
  33. 33.
    Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006;10(6):515–27. doi: 10.1016/j.ccr.2006.10.008.PubMedCrossRefGoogle Scholar
  34. 34.
    Goepfert TM, McCarthy M, Kittrell FS, Stephens C, Ullrich RL, Brinkley BR, et al. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. FASEB J. 2000;14(14):2221–9. doi: 10.1096/fj.00-0165com.PubMedCrossRefGoogle Scholar
  35. 35.
    Pati D, Haddad BR, Haegele A, Thompson H, Kittrell FS, Shepard A, et al. Hormone-induced chromosomal instability in p53-null mammary epithelium. Cancer Res. 2004;64(16):5608–16. doi: 10.1158/0008-5472.CAN-03-0629.PubMedCrossRefGoogle Scholar
  36. 36.
    Weaver Z, Montagna C, Xu X, Howard T, Gadina M, Brodie SG, et al. Mammary tumors in mice conditionally mutant for Brca1 exhibit gross genomic instability and centrosome amplification yet display a recurring distribution of genomic imbalances that is similar to human breast cancer. Oncogene. 2002;21(33):5097–107. doi: 10.1038/sj.onc.1205636.PubMedCrossRefGoogle Scholar
  37. 37.
    Li JJ, Weroha SJ, Lingle WL, Papa D, Salisbury JL, Li SA. Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats. Proc Natl Acad Sci USA. 2004;101(52):18123–8. doi: 10.1073/pnas.0408273101.PubMedCrossRefGoogle Scholar
  38. 38.
    Namba R, Maglione JE, Davis RR, Baron CA, Liu S, Carmack CE, et al. Heterogeneity of mammary lesions represent molecular differences. BMC Cancer. 2006;6:275. doi: 10.1186/1471-2407-6-275.PubMedCrossRefGoogle Scholar
  39. 39.
    Milliken EL, Lozada KL, Johnson E, Landis MD, Seachrist DD, Whitten I, et al. Ovarian hyperstimulation induces centrosome amplification and aneuploid mammary tumors independently of alterations in p53 in a transgenic mouse model of breast cancer. Oncogene. 2008;27(12):1759–66. doi: 10.1038/sj.onc.1210815.PubMedCrossRefGoogle Scholar
  40. 40.
    Suizu F, Ryo A, Wulf G, Lim J, Lu KP. Pin1 regulates centrosome duplication, and its overexpression induces centrosome amplification, chromosome instability, and oncogenesis. Mol Cell Biol. 2006;26(4):1463–79. doi: 10.1128/MCB.26.4.1463-1479.2006.PubMedCrossRefGoogle Scholar
  41. 41.
    Chester N, Babbe H, Pinkas J, Manning C, Leder P. Mutation of the murine Bloom’s syndrome gene produces global genome destabilization. Mol Cell Biol. 2006;26(17):6713–26. doi: 10.1128/MCB.00296-06.PubMedCrossRefGoogle Scholar
  42. 42.
    Medina D, Kittrell FS, Shepard A, Stephens LC, Jiang C, Lu J, et al. Biological and genetic properties of the p53 null preneoplastic mammary epithelium. FASEB J. 2002;16(8):881–3.PubMedGoogle Scholar
  43. 43.
    Li Y, Zhang Y, Hill J, Kim HT, Shen Q, Bissonnette RP, et al. The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice. Br J Cancer. 2008;98(8):1380–8. doi: 10.1038/sj.bjc.6604320.PubMedCrossRefGoogle Scholar
  44. 44.
    Maglione JE, Moghanaki D, Young LJ, Manner CK, Ellies LG, Joseph SO, et al. Transgenic Polyoma middle-T mice model premalignant mammary disease. Cancer Res. 2001;61(22):8298–305.PubMedGoogle Scholar
  45. 45.
    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. 2000;19(8):1028–37. doi: 10.1038/sj.onc.1203281.PubMedCrossRefGoogle Scholar
  46. 46.
    Jones RA, Campbell CI, Gunther EJ, Chodosh LA, Petrik JJ, Khokha R, et al. Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene. 2007;26(11):1636–44. doi: 10.1038/sj.onc.1209955.PubMedCrossRefGoogle Scholar
  47. 47.
    D’Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, et al. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med. 2001;7(2):235–9. doi: 10.1038/84691.PubMedCrossRefGoogle Scholar
  48. 48.
    Debies MT, Gestl SA, Mathers JL, Mikse OR, Leonard TL, Moody SE, et al. 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. 2008;118(1):51–63. doi: 10.1172/JCI33320.PubMedCrossRefGoogle Scholar
  49. 49.
    Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, et al. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev. 2003;17(4):488–501. doi: 10.1101/gad.1051603.PubMedCrossRefGoogle Scholar
  50. 50.
    Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell. 2002;2(6):451–61. doi: 10.1016/S1535-6108(02)00212-X.PubMedCrossRefGoogle Scholar
  51. 51.
    Damonte P, Gregg JP, Borowsky AD, Keister BA, Cardiff RD. EMT tumorigenesis in the mouse mammary gland. Lab Invest. 2007;87(12):1218–26. doi: 10.1038/labinvest.3700683.PubMedCrossRefGoogle Scholar
  52. 52.
    Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442–54. doi: 10.1038/nrc822.PubMedCrossRefGoogle Scholar
  53. 53.
    Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42. doi: 10.1038/nrm1835.PubMedCrossRefGoogle Scholar
  54. 54.
    Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 2005;8(3):197–209. doi: 10.1016/j.ccr.2005.07.009.PubMedCrossRefGoogle Scholar
  55. 55.
    Wang W, Goswami S, Lapidus K, Wells AL, Wyckoff JB, Sahai E, et al. Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res. 2004;64(23):8585–94. doi: 10.1158/0008-5472.CAN-04-1136.PubMedCrossRefGoogle Scholar
  56. 56.
    Wang W, Wyckoff JB, Frohlich VC, Oleynikov Y, Huttelmaier S, Zavadil J, et al. Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res. 2002;62(21):6278–88.PubMedGoogle Scholar
  57. 57.
    Wang W, Wyckoff JB, Goswami S, Wang Y, Sidani M, Segall JE, et al. Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res. 2007;67(8):3505–11. doi: 10.1158/0008-5472.CAN-06-3714.PubMedCrossRefGoogle Scholar
  58. 58.
    Menard S, Aiello P, Tagliabue E, Rumio C, Lollini PL, Colnaghi MI, et al. Tamoxifen chemoprevention of a hormone-independent tumor in the proto-neu transgenic mice model. Cancer Res. 2000;60(2):273–5.PubMedGoogle Scholar
  59. 59.
    Namba R, Young LJ, Maglione JE, McGoldrick ET, Liu S, Wurz GT, et al. Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ. Breast Cancer Res. 2005;7(6):R881–889. doi: 10.1186/bcr1317.PubMedCrossRefGoogle Scholar
  60. 60.
    Yoshidome K, Shibata MA, Couldrey C, Korach KS, Green JE. 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. 2000;60(24):6901–10.PubMedGoogle Scholar
  61. 61.
    Li Y, Zhang Y, Hill J, Shen Q, Kim HT, Xu X, et al. The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice. Clin Cancer Res. 2007;13(20):6224–31. doi: 10.1158/1078–0432.CCR-06–2681.PubMedCrossRefGoogle Scholar
  62. 62.
    Wu K, Kim HT, Rodriquez JL, Hilsenbeck SG, Mohsin SK, Xu XC, et al. Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069. Cancer Epidemiol Biomarkers Prev. 2002;11(5):467–74.PubMedGoogle Scholar
  63. 63.
    Basu GD, Pathangey LB, Tinder TL, Lagioia M, Gendler SJ, Mukherjee P. Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer. Mol Cancer Res. 2004;2(11):632–42.PubMedGoogle Scholar
  64. 64.
    Yoshinaka R, Shibata MA, Morimoto J, Tanigawa N, Otsuki Y. COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine mammary cancer. Anticancer Res. 2006;26(6B):4245–54.PubMedGoogle Scholar
  65. 65.
    Lu C, Speers C, Zhang Y, Xu X, Hill J, Steinbis E, et al. Effect of epidermal growth factor receptor inhibitor on development of estrogen receptor-negative mammary tumors. J Natl Cancer Inst. 2003;95(24):1825–33.PubMedGoogle Scholar
  66. 66.
    Piechocki MP, Dibbley SK, Lonardo F, Yoo GH. Gefitinib prevents cancer progression in mice expressing the activated rat HER2/neu. Int J Cancer. 2008;122(8):1722–9. doi: 10.1002/ijc.23231.PubMedCrossRefGoogle Scholar
  67. 67.
    Medina D, Lane HW. Stage specificity of selenium-mediated inhibition of mouse mammary tumorigenesis. Biol Trace Elem Res. 1983;5:297–306.CrossRefGoogle Scholar
  68. 68.
    Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO, Perou CM, et al. FOXA1 expression in breast cancer–correlation with luminal subtype A and survival. Clin Cancer Res. 2007;13(15 Pt 1):4415–21. doi: 10.1158/1078-0432.CCR-07-0122.PubMedCrossRefGoogle Scholar
  69. 69.
    Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14(5):1368–76. doi: 10.1158/1078-0432.CCR-07-1658.PubMedCrossRefGoogle Scholar
  70. 70.
    Hannemann J, Velds A, Halfwerk JB, Kreike B, Peterse JL, van de Vijver MJ. Classification of ductal carcinoma in situ by gene expression profiling. Breast Cancer Res. 2006;8(5):R61. doi: 10.1186/bcr1613.PubMedCrossRefGoogle Scholar
  71. 71.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52. doi: 10.1038/35021093.PubMedCrossRefGoogle Scholar
  72. 72.
    Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98(19):10869–74. doi: 10.1073/pnas.191367098.PubMedCrossRefGoogle Scholar
  73. 73.
    Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100(14):8418–23. doi: 10.1073/pnas.0932692100.PubMedCrossRefGoogle Scholar
  74. 74.
    van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009. doi: 10.1056/NEJMoa021967.PubMedCrossRefGoogle Scholar
  75. 75.
    Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 2007;8(5):R76. doi: 10.1186/gb-2007-8-5-r76.PubMedCrossRefGoogle Scholar
  76. 76.
    Deeb KK, Michalowska AM, Yoon CY, Krummey SM, Hoenerhoff MJ, Kavanaugh C, et al. Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis. Cancer Res. 2007;67(17):8065–80. doi: 10.1158/0008-5472.CAN-07-1515.PubMedCrossRefGoogle Scholar
  77. 77.
    Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, 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. 2006;10(5):437–49. doi: 10.1016/j.ccr.2006.09.013.PubMedCrossRefGoogle Scholar
  78. 78.
    Kim HJ, Litzenburger BC, Cui X, Delgado DA, Grabiner BC, Lin X, et al. Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol. 2007;27(8):3165–75. doi: 10.1128/MCB.01315-06.PubMedCrossRefGoogle Scholar
  79. 79.
    Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, et al. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol. 2006;26(24):9302–14. doi: 10.1128/MCB.00260-06.PubMedCrossRefGoogle Scholar
  80. 80.
    Morris VL, Koop S, MacDonald IC, Schmidt EE, Grattan M, Percy D, et al. Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth. Clin Exp Metastasis. 1994;12(6):357–67. doi: 10.1007/BF01755879.PubMedCrossRefGoogle Scholar
  81. 81.
    Lelekakis M, Moseley JM, Martin TJ, Hards D, Williams E, Ho P, et al. A novel orthotopic model of breast cancer metastasis to bone. Clin Exp Metastasis. 1999;17(2):163–70. doi: 10.1023/A:1006689719505.PubMedCrossRefGoogle Scholar
  82. 82.
    et al. Blocking tumor growth, invasion, and metastasis by maspin in a syngeneic breast cancer model. Cancer Res. 2001;61(18):6945–51.PubMedGoogle Scholar
  83. 83.
    Li Z, Schem C, Shi YH, Medina D, Zhang M. Increased COX2 expression enhances tumor-induced osteoclastic lesions in breast cancer bone metastasis. Clin Exp Metastasis 2007;25(4):389–400.PubMedCrossRefGoogle Scholar
  84. 84.
    Bissell MJ, Kenny PA, Radisky DC. Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes. Cold Spring Harb Symp Quant Biol. 2005;70:343–56. doi: 10.1101/sqb.2005.70.013.PubMedCrossRefGoogle Scholar
  85. 85.
    Nelson CM, Inman JL, Bissell MJ. Three-dimensional lithographically defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression. Nat Protocols. 2008;3(4):674–8. doi: 10.1038/nprot.2008.35.CrossRefGoogle Scholar
  86. 86.
    Barcellos-Hoff MH, Ravani SA. Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res. 2000;60(5):1254–60.PubMedGoogle Scholar
  87. 87.
    Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, et al. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA. 2004;101(14):4966–71. doi: 10.1073/pnas.0401064101.PubMedCrossRefGoogle Scholar
  88. 88.
    Lin EY, Pollard JW. Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer. 2004;90(11):2053–8. doi: 10.1038/sj.bjc.6601705.PubMedCrossRefGoogle Scholar
  89. 89.
    Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124(2):263–6. doi: 10.1016/j.cell.2006.01.007.PubMedCrossRefGoogle Scholar
  90. 90.
    Lin EY, Pollard JW. Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Res. 2007;67(11):5064–6. doi: 10.1158/0008-5472.CAN-07-0912.PubMedCrossRefGoogle Scholar
  91. 91.
    Hawsawi NM, Ghebeh H, Hendrayani SF, Tulbah A, Al-Eid M, Al-Tweigeri T, et al. Breast carcinoma-associated fibroblasts and their counterparts display neoplastic-specific changes. Cancer Res. 2008;68(8):2717–25. doi: 10.1158/0008-5472.CAN-08-0192.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Cellular and Molecular BiologyBaylor College of MedicineHoustonUSA

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