Skip to main content
SpringerLink
Log in

Transgenic mouse models of breast cancer

  • Transgenic mouse models
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Although valuable initial information can be gathered about transformation fromin vitro studies, human cancer occurs in the context of a complex interaction with its environment and must ultimately be studied in living animals. Transgenic animal models have been used to study breast transformation for a number of years and have yielded valuable information on the subject. In this paper, we will summarize results from our laboratories, and others, regarding the use of transgenic mice to study breast tumorigenesis. We will also suggest future directions for the use of transgenic models to understand, and hopefully, one day to cure the disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jaenisch R: Transgenic animals. Science 240:1468–1474, 1988

    PubMed  Google Scholar 

  2. Merlino G: Transgenic mice as models for tumorigenesis. Cancer Inv 12:203–213, 1994

    Google Scholar 

  3. Frohman MA, Martin GR: Cut, paste and save: New approaches to altering specific genes in mice. Cell 56:145–147, 1989

    PubMed  Google Scholar 

  4. De Larco JE, Todaro GJ: Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci USA 75:4001–4005, 1978

    PubMed  Google Scholar 

  5. Derynck R, Roberts AB, Winkler ME, Chen EY, Goeddel DV: Human transforming growth factor-α: precursor structure and expression in E. coli. Cell 38:287–297, 1984

    PubMed  Google Scholar 

  6. Massague J: Epidermal growth factor-like transforming growth factor. J Biol Chem 258:13614–13620, 1983

    PubMed  Google Scholar 

  7. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, Berger WH: Synthesis of messenger RNAs for transforming growth factors α and ß and the epidermal growth factor receptor by human tumors. Cancer Res 47:707–712, 1987

    PubMed  Google Scholar 

  8. Bates SE, Davidson NE, Valverius EM, Freter CE, Dickson RB, Tam JP, Kudlow JE, Lippman ME, Salomon DS: Expression of transforming growth factor α and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Mol Endocrinol 2:543–555, 1988

    PubMed  Google Scholar 

  9. Perroteau I, Salomon D, DeBortoli M, Kidwell W, Hazarika P, Pardue R, Dedman J, Tam J: Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat 7:201–210, 1986

    PubMed  Google Scholar 

  10. Travers MT, Barrett-Lee PJ, Berger U, Luqmani YA, Gazet JC, Powles TJ, Coombes RC: Growth factor expression in normal, benign, and malignant breast tissue. Br Med J 296:1621–1624, 1988

    Google Scholar 

  11. Arteaga CL, Hanauske AR, Clark GM, Osborne K, Hazarika P, Pardue RL, Tio F, Von Hoff DD: Immunoreactive α transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patient prognosis. Cancer Res 48:5023–5028, 1988

    PubMed  Google Scholar 

  12. Macias A, Perez R, Hagerstrom T, Skoog L: Identification of transforming growth factor alpha in human primary breast carcinomas. Anticancer Res 7:1271–1280, 1987

    PubMed  Google Scholar 

  13. Normanno N, Qi CF, Gullick WJ, Persico G, Yarden Y, Wen D, Plowman G, Kenney N, Johnson G, Kim N, Brandt R, Martinez-Lacaci I, Dickson RB, Salomon DS: Expression of amphiregulin, cripto-1, and heregulin α in human breast cancer cells. Int J Oncol 2:903–911, 1993

    Google Scholar 

  14. LeJeune S, Leek R, Horak E, Plowman G, Greenall M, Harris AL: Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. Cancer Res 53:3597–3602, 1993

    PubMed  Google Scholar 

  15. Harris AL, Nicholson S: Epidermal growth factor receptors in human breast cancer.In: Lippman ME, Dickson RB (eds) Breast Cancer: Cellular and Molecular Biology. Kluwer, Boston, 1988, pp 93–118

    Google Scholar 

  16. Jhappan C, Stahle C, Harkins RN, Fausto N, Smith GH, Merlino GT: TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61:1137–1146, 1990

    PubMed  Google Scholar 

  17. Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC: Overexpression of TGFα in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61:1121–1135, 1990

    PubMed  Google Scholar 

  18. Matsui Y, Halter SA, Holt JT, Hogan BLM, Coffey RJ: Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice. Cell 61:1147–1155, 1990

    PubMed  Google Scholar 

  19. Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J: The SH2 and SH3 domain containing protein Grb2 links receptor tyrosine kinases to ras signalling. Cell 70:431–442, 1992

    PubMed  Google Scholar 

  20. Buday L, Downward J: Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73:611–620, 1993

    PubMed  Google Scholar 

  21. Margolis B, Li N, Koch A, Mohammadi M, Hurwitz DR, Zilberstein A, Ullrich A, Pawson T, Schlessinger J: The tyrosine phosphorylated carboxyterminus of the EGF-receptor is a binding site for GAP and PLC-γ. EMBO J 9:4375–4380, 1990

    PubMed  Google Scholar 

  22. Margolis B, Bellot AM, Honegger AM, Ullrich A, Schlessinger J, Zilberstein A: Tyrosine kinase activity is essential for the association of phospholipase C-γ with the epidermal growth factor receptor. Mol Cell Biol 10:435–441, 1990

    PubMed  Google Scholar 

  23. Hu B, Margolis B, Skolnik EY, Lammers R, Ullrich A, Schlessinger J: Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Mol Cell Biol 12:981–990, 1992

    PubMed  Google Scholar 

  24. Rozakis-Adcock M, McGlade MJ, Mbamalu G, Pelicci G, Daly RD, Li W, Batzer AG, Thomas S, Brugge J, Pelicci PG, Schlessinger J, Pawson T: Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature (London) 360:689–692, 1992

    Google Scholar 

  25. Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, Weinberg RA: Theneu oncogene: anerb-B-related gene encoding a 185,000-Mr tumor antigen. Nature 312:513–516, 1984

    PubMed  Google Scholar 

  26. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson A, Ullrich A: Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location withneu oncogene. Science 230:1132–1139, 1985

    PubMed  Google Scholar 

  27. Semba K, Kamata N, Toyoshima K, Yamamoto T: A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82:6497–6501, 1985

    PubMed  Google Scholar 

  28. Bargmann CI, Hung M, Weinberg RA: Theneu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319:226–230, 1986

    PubMed  Google Scholar 

  29. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of protein encoded by the human c-erb-B-2 gene to the epidermal growth factor receptor. Nature 319:230–234, 1986

    PubMed  Google Scholar 

  30. Bargmann CI, Hung M, Weinberg RA: Multiple independent activations of theneu oncogene by a point mutation altering the transmembrane domain of p185. Cell 45:649–657, 1986

    PubMed  Google Scholar 

  31. Weiner DB, Liu J, Cohen JA, Williams WV, Greene MI: A point mutation on theneu oncogene mimics ligand induction of receptor aggregation. Nature 339:230–231, 1989

    PubMed  Google Scholar 

  32. Sternberg MJE, Gullick WJ: Neu receptor dimerization. Nature 339:587, 1989

    PubMed  Google Scholar 

  33. Stern DF, Kamps MP, Cao H: Oncogenic activation of p185neu stimulates tyrosine kinase phosphorylation in vivo. Mol Cell Biol 8:3969–3973, 1988

    PubMed  Google Scholar 

  34. Lemoine NR, Staddon S, Dickson C, Barnes DM, Gullick WJ: Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene 5:237–239, 1990

    PubMed  Google Scholar 

  35. King CR, Kraus MH, Aaronson SA: Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229:974–976, 1985

    PubMed  Google Scholar 

  36. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of theHER-2/neu oncogene. Science 235:177–182, 1987

    PubMed  Google Scholar 

  37. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712, 1989

    PubMed  Google Scholar 

  38. Berger MS, Locher GW, Saurer S, Gullick WJ, Waterfield MD, Groner B, Hynes NE: Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res 48:1238–1243, 1988

    PubMed  Google Scholar 

  39. Tavassoli M, Quirke P, Farzaneh F, Lock NJ, Mayne LV, Kirkham N: c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumor grade, in human breast carcinoma. Br J Cancer 60:505–510, 1989

    PubMed  Google Scholar 

  40. Iglehart D, Kraus MH, Langton BC, Huper G, Kerns BJ, Marks JR: IncreasederbB-2 gene copies and expression in multiple stages of breast cancer. Cancer Res 50:6701–6707, 1990

    PubMed  Google Scholar 

  41. Gullick WJ: The role of the epidermal growth factor receptor and the c-erbB-2 protein in breast cancer. Int J Cancer Suppl 5:55–61, 1990

    PubMed  Google Scholar 

  42. Perren TJ: c-erbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer 63:328–332, 1991

    PubMed  Google Scholar 

  43. Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR: Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erB2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112, 1990

    PubMed  Google Scholar 

  44. Guy C, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ: Expression of theneu oncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 89:10578–10582, 1992

    PubMed  Google Scholar 

  45. Bouchard L, Lamarre L, Tremblay PJ, Jolicoeur P: Stochastic appearance of mammary tumors on transgenic mice carrying the MMTV/c-neu oncogene. Cell 57:931–936, 1989

    PubMed  Google Scholar 

  46. Cardiff RD, Sinn E, Muller W, Leder P: Transgenic oncogenic mice: tumor phenotype predicts genotype. Am J Pathology 139:495–501, 1991

    Google Scholar 

  47. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P: Single step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54:105–115, 1988

    PubMed  Google Scholar 

  48. Lucchini F, Sacco MG, Hu N, Villa A, Brown J, Cesano L, Mangiarini L, Rindi G, Kindl S, Sessa F, Vezzoni P, Clerici L: Early and multifocal tumors in breast, salivary, Harderian and epididymal tissues developed in MMTV-Neu transgenic mice. Cancer Letters 64:203–209, 1992

    PubMed  Google Scholar 

  49. Muthuswamy SK, Siegel PM, Dankort DL, Webster MA, Muller WA: Mammary tumors expressing theneu proto-oncogene possess elevated c-Src tyrosine kinase activity. Mol Cell Biol 14:735–743, 1994

    PubMed  Google Scholar 

  50. Kato GJ, Dang CV: Function of the c-Myc oncoprotein. FASEB J 6:3065–3072, 1992

    PubMed  Google Scholar 

  51. Meichle A, Philipp A, Eilers M: The functions of the Myc proteins. Biochim Biophys Acta 1114:129–146, 1992

    PubMed  Google Scholar 

  52. Landschulz WH, Johnson PF, McKnight SL: The leucine zipper: A hypothetical structure common to a new class of DNA binding proteins. Science 240:1759–1764, 1988

    PubMed  Google Scholar 

  53. Murre C, McCaw PS, Baltimore D: A new DNA binding and dimerization motif in immunoglobulin enhancer binding,daughterless, myoD, andmyc proteins. Cell 56:777–783, 1989

    PubMed  Google Scholar 

  54. Prendergast GC, Ziff EB: DNA-binding motif. Nature 341:392, 1989

    Google Scholar 

  55. Blackwood EM, Eisenman RN: Max: a helix-loophelix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251:1211–1217, 1991

    PubMed  Google Scholar 

  56. Cole MD: Myc meets its Max. Cell 65:715–716, 1991

    PubMed  Google Scholar 

  57. Prendergast GC, Lawe D, Ziff EB: Association of Myn, the murine homologue of Max, with c-Myc stimulates methylation-sensitive DNA binding and Ras cotransformation. Cell 65:395–407, 1991

    PubMed  Google Scholar 

  58. Bonilla M, Ramirez M, Lopez-Cueto J, Gariglio P: In vivo amplification and rearrangement of c-myc oncogene in human breast tumors. J Natl Cancer Inst 80:665–671, 1988

    PubMed  Google Scholar 

  59. Escot C, Theillet C, Lidereau R, Spyratos F, Champeme M, Gest J, Callahan R: Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci USA 83:4834–4838, 1986

    PubMed  Google Scholar 

  60. Garcia I, Dietrich PY, Aapro M, Vauthier G, Vadas L, Engel E: Genetic alteration of c-myc, c-erbB-2 and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. Cancer Res 49:6675–6679, 1989

    PubMed  Google Scholar 

  61. Mariani-Costantini R, Escot C, Theillet C, Gentile A, Merlo G, Lidereau R, Callahan R:In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast. Cancer Res 48:199–205, 1988

    PubMed  Google Scholar 

  62. Borg A, Baldetorp B, Ferno M, Olsson H, Sigurdsson H: c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. Int J Cancer 51:687–691, 1992

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  64. Leder A, Pattengale PK, Kuo A, Stewart T, Leder P: Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 45:485–495, 1986

    PubMed  Google Scholar 

  65. Schoenenberger CA, Andres AC, Groner B, van der Valk M, Lemeur M, Gerlinger P: Targeted c-myc gene expression in mammary glands of transgenic mice induces mammary tumors with constitutive milk protein gene transcription. EMBO J 7:169–175, 1988

    PubMed  Google Scholar 

  66. Edwards PA, Ward JL, Bradbury JM: Alteration of morphogenesis by the v-myc oncogene in transplants of mammary gland. Oncogene 2:407–412, 1988

    PubMed  Google Scholar 

  67. Vonderhaar BK: Regulation of development of the normal mammary gland by hormones and growth factors.In: Lippman ME, Dickson RB (eds) Breast Cancer: Cellular and Molecular Biology. Kluwer Academic Publishers, Norwell MA, 1988, pp 251–266

    Google Scholar 

  68. DeOme KB, Faulkin LJ, Bern HA, Blair PB: Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free fat pads of female C3H mice. Cancer Res 19:515–520, 1959

    PubMed  Google Scholar 

  69. Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S: Oncogenes and signal transduction. Cell 64:281–302, 1991

    PubMed  Google Scholar 

  70. Courtniedge SA: Activation of pp60c-src kinase by middle T or by dephosphorylation. EMBO J 4:1471–1477, 1985

    PubMed  Google Scholar 

  71. Kornbluth S, Sudol M, Hanafusa H: Association of polyomavirus middle-T antigen with c-yes protein. Nature (London) 325:171–173, 1987

    Google Scholar 

  72. Jacobs C, Rubsamen H: Expression of pp60c-src protein kinase in adult and fetal human tissue: high activity in some sarcomas and mammary carcinomas. Cancer Res 43:1696–1702, 1983

    PubMed  Google Scholar 

  73. Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA: Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem 262:13754–13759, 1986

    Google Scholar 

  74. Ottenhoff-Kalff AE, Rijksen G, van Beurden EACM, Hennipman A, Michels AA, Staal GEJ: Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product. Cancer Res 52:4773–4778, 1992

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  76. Guy CT, Muthuswamy SK, Cardiff RD, Soriano P, Muller WJ: Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev 8:23–32, 1994

    PubMed  Google Scholar 

  77. Levine AJ: The tumor suppressor genes. Ann Rev Biochem 62:623–651, 1993

    PubMed  Google Scholar 

  78. Tzeng Y, Guhl E, Graessmann M, Graessmann A: Breast cancer formation in transgenic animal induced by the whey acidic protein SV40T antigen (WAP-SV-T) hybrid gene. Oncogene 8:1965–1971, 1993

    PubMed  Google Scholar 

  79. Moodie SA, Wolfman A: The 3Rs of life: Ras, Raf and growth regulation. Trends Genet 10:44–48, 1994

    PubMed  Google Scholar 

  80. Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA: Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature 363:45–51, 1993

    PubMed  Google Scholar 

  81. Hand PH, Thor A, Wunderlich D, Muraro R, Caruso A, Schlom J: Monoclonal antibodies of predefined specificity detect activatedras gene expression in human mammary and colon carcinomas. Proc Natl Acad Sci USA 81:5227–5231, 1984

    PubMed  Google Scholar 

  82. DeBortoli ME, Abou-Issa H, Haley BE, Cho-Chung YS: Amplified expression of p21ras protein in hormone-dependent mammary carcinomas of humans and rodents. Biochem Biophys Res Commun 127:699–706, 1985

    PubMed  Google Scholar 

  83. Slamon DJ, DeKernion JB, Verma IM, Cline MJ: Expression of cellular oncogenes in human malignancies. Science 224:256–262, 1984

    PubMed  Google Scholar 

  84. Theillet C, Liderau R, Escot C, Hutzell P, Brunet M, Gest J, Schlom J, Callahan R: Loss of a c-H-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res 46:4776–4781, 1986

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  86. Tremblay PJ, Pothier F, Hoang T, Tremblay G, Brownstein S, Liszauer A, Jolicoeur P: Transgenic mice carrying the mouse mammary tumor virusras fusion gene: distinct effects in various tissues. Mol Cell Biol 9:854–859, 1989

    PubMed  Google Scholar 

  87. Andres A, Schonenberger C, Groner B, Henninghausen L, LeMeur M, Gerlinger P: Ha-ras oncogene expression directed by a milk protein gene promoter: Tissue specificity, hormonal regulation, and tumor induction in transgenic mice. Proc Natl Acad Sci USA 84:1299–1303, 1987

    PubMed  Google Scholar 

  88. Nusse R: The activation of cellular oncogenes by proviral insertion in murine mammary cancer.In: Lippman ME, Dickson RB (eds) Breast Cancer: Cellular and Molecular Biology. Kluwer Academic Publishers, Norwell MA, 1988, pp 283–306

    Google Scholar 

  89. Wilkinson DG, Peters G, Dickson C, McMahon AP: Expression of the FGF-related proto-oncogeneint-2 during gastrulation and neurulation in the mouse. EMBO J 7:691–695, 1988

    PubMed  Google Scholar 

  90. Dickson C, Fantl V: Fgf-3, an oncogene in murine breast cancer.In: Lippman ME, Dickson RB (eds) Mammary Tumorigenesis and Malignant Progression. Kluwer Academic Publishers, Norwell MA, 1994, pp 331–344

    Google Scholar 

  91. Tsukamoto AS, Grosschedl R, Guman RC, Parslow T, Varmus HE: Expression of theint-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55:619–625, 1988

    PubMed  Google Scholar 

  92. Stamp G, Fantl V, Poulsom R, Jamieson S, Smith R, Peters G, Dickson S: Non-uniform expression of a mouse mammary tumor virus-drivenint-2/fgf-3 transgene in pregnancy-responsive breast-tumors. Cell Growth Differ 3:929–938, 1992

    PubMed  Google Scholar 

  93. Muller WJ, Lee FS, Dickson C, Peters G, Pattengale P, Leder P: The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J 9:907–913, 1990

    PubMed  Google Scholar 

  94. Robbins J, Blondel B, Gallahan D, Callahan R: Mouse mammary tumor geneint-3: a member of the notch gene family transforms mammary epithelial cells. J Virol 66:2594–2599, 1992

    PubMed  Google Scholar 

  95. Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R: Expression of an activatednotch-relatedint-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev 6:345–355, 1992

    PubMed  Google Scholar 

  96. Nigro JM, Baker, SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B: Mutations in the p53 gene occur in diverse human tumor types. Nature 342:705–708, 1989

    PubMed  Google Scholar 

  97. Allred DC, Elledge R, Clark GM, Fuqua SAW: The p53 tumor suppressor gene in human breast cancer.In: Lippman ME, Dickson RB (eds) Mammary Tumorigenesis and Malignant Progression. Kluwer Academic Publishers, Norwell MA, 1994, pp 63–77

    Google Scholar 

  98. Silvestrini R, Benini E, Daidone MG, Veneroni S, Boracchi P, Cappelletti V, Di Fronzo G, Veronesi U: p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst 85:965–970, 1993

    PubMed  Google Scholar 

  99. Allred DC, Clark GM, Elledge R, Fuqua SAW, Brown RW, Chamness GC, Osborne CK, McGuire WL: Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85:200–206, 1993

    PubMed  Google Scholar 

  100. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Butel JS, Bradley A: Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356:215–221, 1992

    PubMed  Google Scholar 

  101. Coles C, Condie A, Chetty U, Steel CM, Evans HJ, Prosser J: p53 mutations in breast cancer. Cancer Res 52:5291–5298, 1992

    PubMed  Google Scholar 

  102. Li B, Greenberg L, Stephens LC, Meyn R, Medina D, Rosen JM: Preferential overexpression of a 172arg-Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development. Cell Growth Differ 5:711–721, 1994

    PubMed  Google Scholar 

  103. Sporn MB, Roberts AB, Wakefield LM, Crombrugghe B: Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105:1039–1045, 1987

    PubMed  Google Scholar 

  104. Silberstein GB, Daniels CW: Reversible inhibition of mammary gland growth by transforming growth factor-β. Science 237:291–293, 1987

    PubMed  Google Scholar 

  105. Jhappan C, Geiser AG, Kordon EC, Bagheri D, Hennighausen L, Roberts AB, Smith GH, Merlino G: Targeting expression of a transforming growth factor ß1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. EMBO J 12:1835–1845, 1993

    PubMed  Google Scholar 

  106. Pierce DF, Johnson MD, Matsui Y, Robinson SD, Gold LI, Purchio AF, Daniel CW, Hogan BL, Moses HL: Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing TGF-beta-1. Genes Dev 7:2308–2317, 1993

    PubMed  Google Scholar 

  107. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T: Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33:389–396, 1983

    PubMed  Google Scholar 

  108. Swenson KI, Farell KM, Ruderman JV: The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. Cell 47:861–870, 1986

    PubMed  Google Scholar 

  109. Standart N, Minshull J, Pines J, Hunt T: Cyclin synthesis, modification and destruction during meiotic maturation of the starfish oocyte. Dev Biol 124:248–258, 1987

    PubMed  Google Scholar 

  110. Draetta G: Cell cycle control in eukaryotes: molecular mechanism of cdc2 activation. Trends Biochem 15:378–383, 1990

    Google Scholar 

  111. Tsai L, Harlow E, Meyerson M: Isolation of the humancdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature 353:174–177, 1991

    PubMed  Google Scholar 

  112. Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G: Cyclin A is required at two points in the human cell cycle. EMBO J 11:961–971, 1992

    PubMed  Google Scholar 

  113. Hunt T: Cell cycle gets more cyclins. Nature 350:462–463, 1991

    PubMed  Google Scholar 

  114. Keyomarsi K, Pardee AB: Redundant cyclin overexpression and gene amplification in breast cancer cells. Proc Natl Acad Sci USA 90:1112–1116, 1993

    PubMed  Google Scholar 

  115. Keyomarsi K, O'Leary N, Molnar G, Lees E, Fingert HJ, Pardee AB: Cyclin E, a potential prognostic marker for breast cancer. Cancer Res 54:380–385, 1994

    PubMed  Google Scholar 

  116. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A: A novel cyclin encoded by abcll-linked candidate oncogene. Nature 350:512–515, 1991

    PubMed  Google Scholar 

  117. Matshushime H, Roussel MF, Ashmun RA, Sherr CJ: Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell 65:701–713, 1991

    PubMed  Google Scholar 

  118. Musgrove EA, Hamilton JA, Lee CSL, Sweeney KJE, Watts CKW, Sutherland RL: Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol Cell Biol 13:3577–3587, 1993

    PubMed  Google Scholar 

  119. Ali IU, Merlo G, Callahan R, Lidereau R: The amplification unit on chromosome 11q13 in aggressive primary human breast tumors entails the bcl-1, int-2 and hst loci. Oncogene 4:89–92, 1989

    PubMed  Google Scholar 

  120. Theillet C, Adane J, Szepetowski P, Simon M, Jeanteur P, Birnbaum D, Gaudray P:BCL-1 participates in the 11q13 amplification found in breast cancer. Oncogene 5:147–149, 1990

    PubMed  Google Scholar 

  121. Buckley MF, Sweeney KJE, Hamilton JA, Sini RL, Manning DJ, Nicholson RI, deFazio A, Watts CKW, Musgrove EA, Sutherland RL: Expression and amplification of cyclin genes in human breast cancer. Oncogene 8:2127–2133, 1993

    PubMed  Google Scholar 

  122. Szepetowski P, Ollemdorff V, Grosgeorge J, Courseaux A, Birnbaum D, Theillet D, Gaudray P: DNA amplification at 11q13.5-q14 in human breast cancer. Oncogene 7:2513–2517, 1993

    Google Scholar 

  123. Lammie GA, Fantl V, Smith R, Schuuring E, Brookes S, Michalides R, Dickson C, Arnold A, Peters G: D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. Oncogene 6:439–444, 1991

    PubMed  Google Scholar 

  124. Schuuring E, Verhoeven E, Mooi WJ, Michalides RJ: Identification and cloning of two overexpressed genes, U21B31/PRAD1 andEMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7:355–361, 1992

    PubMed  Google Scholar 

  125. Jiang W, Kahn SM, Tomita N, Zhang Y, Lu S, Weinstein IB: Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 52:2980–2983, 1992

    PubMed  Google Scholar 

  126. Wang TC, Cardiff R, Zukerberg L, Lees E, Arnold A, Schmidt EV: Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 366:669–671, 1994

    Google Scholar 

  127. van Lohuizen M, Verbeek S, Krimpenfort P, Domen J, Saris C, Radaszkiewicz T, Berns A: Predisposition to lymphomagenesis inpim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell 56:673–682, 1989

    PubMed  Google Scholar 

  128. van Lohuizen M, Verbeek S, Scheijen B, Wientjens E, van der Gulden H, Berns A: Identification of cooperating oncogenes in Eu-myc transgenic mice by provirus tagging. Cell 65:737–752, 1991

    PubMed  Google Scholar 

  129. Haupt Y, Alexander WS, Barri G, Klinken LP, Adams JM: Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Eu-myc transgenic mice. Cell 65:753–763, 1991

    PubMed  Google Scholar 

  130. Hunter T: Cooperation between oncogenes. Cell 64:249–270, 1991

    PubMed  Google Scholar 

  131. Kwan H, Pecenka V, Tsukamoto A, Parslow TG, Guzman R, Lin T, Muller WJ, Lee FS, Leder P, Varmus HE: Transgenes expressing thewnt-1 andint-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Mol Cell Biol 12:147–154, 1992

    PubMed  Google Scholar 

  132. Shackleford GM, MacArthur CA, Kwan HC, Varmus HE: Mouse mammary tumor virus infection accelerates mammary carcinogenesis inwnt-1 transgenic mice by insertional activation ofint-1/fgf-3 andhst/fgf-4. Proc Natl Acad Sci USA 90:740–744, 1993

    PubMed  Google Scholar 

  133. Amundadottir LT, Johnson MD, Merlino G, Smith G, Dickson RB: Synergistic interaction of TGFα and c-myc in mouse mammary gland tumorigenesis. Cell Growth and Diff 6:737–748, 1995

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vincent T. Lombardi Cancer Center, The Research Building, Georgetown University, 3970 Reservoir Road, 20007, Washington D.C, NW, USA

    Laufey T. Amundadottir & Robert B. Dickson

  2. Department of Cell Biology, Georgetown University, 20007, Washington DC, USA

    Laufey T. Amundadottir & Robert B. Dickson

  3. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA

    Glenn Merlino

Authors
  1. Laufey T. Amundadottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Glenn Merlino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert B. Dickson
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Note: genes are referred to as lowercase names in italics (e.g.myc) and their protein products as uppercase (e.g. Myc).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amundadottir, L.T., Merlino, G. & Dickson, R.B. Transgenic mouse models of breast cancer. Breast Cancer Res Tr 39, 119–135 (1996). https://doi.org/10.1007/BF01806083

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01806083

Key words

Search

Navigation