Breast Cancer Research and Treatment

, Volume 113, Issue 1, pp 1–8 | Cite as

A spontaneous estrogen dependent, tamoxifen sensitive mouse mammary tumor: a new model system to study hormone-responsiveness in immune competent mice

  • Marina Simian
  • Teresita Manzur
  • Vanina Rodriguez
  • Elisa Bal de Kier Joffé
  • Slobodanka Klein
Preclinical Study


Currently, an in vivo spontaneous model of estrogen dependent, tamoxifen sensitive breast cancer does not exist. We show here the characterization of the M05 mammary tumor that appeared spontaneously in a 1-year-old virgin female BALB/c mouse in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. When it was transplanted to either male or ovariectomized female mice it did not grow. Moreover, ovariectomy or treatment with tamoxifen of tumor bearing mice led to a halt in tumor growth. Treatment of ovariectomized mice that had been inoculated with the M05 tumor showed that only estradiol, but not progesterone, promoted the re-growth of the tumor. Finally, after passage nine, tumor growth was achieved in male and ovariectomized female mice suggesting that the tumor had progressed to hormone independence. However, like often found in the clinic, expression of estrogen and progesterone receptors was maintained. This model mimics the biology of estrogen receptor positive breast cancer in humans and presents itself as an invaluable tool for the study of endocrine resistance in a physiologically relevant setting.


Breast cancer Estrogen dependent Tamoxifen sensitive In vivo mouse model 



We thank Isabel Stillitani and Liliana Vauthay for excellent technical assistance, and Dr. Gorostidy for her contribution to the pathological characterization of the tumor. This work was supported by a grant of the Susan G. Komen For The Cure to Marina Simian and grants M068 (UBACyT) and PICT 14088 (BID 1728/OC-AR, ANCyT) to Elisa Bal de Kier Joffé.


  1. 1.
    Barcellos-Hoff MH, Ravani SA (2000) Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 60:1254–1260PubMedGoogle Scholar
  2. 2.
    Beatson GT (1896) On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 2:104–107CrossRefGoogle Scholar
  3. 3.
    Clarke RB (2003) Steroid receptors and proliferation in the human breast. Steroids 68:789–794PubMedCrossRefGoogle Scholar
  4. 4.
    Denardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9:212PubMedCrossRefGoogle Scholar
  5. 5.
    Dowsett M, Folkerd E, Doody D, Haynes B (2005) The biology of steroid hormones and endocrine treatment of breast cancer. Breast 14:452–457PubMedCrossRefGoogle Scholar
  6. 6.
    Engel LW, Young NA, Tralka TS, Lippman ME, O’Brien SJ, Joyce MJ (1978) Establishment and characterization of three new continuous cell lines derived from human breast carcinomas. Cancer Res 38:3352–3364PubMedGoogle Scholar
  7. 7.
    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 12:954–961PubMedGoogle Scholar
  8. 8.
    Institute of Laboratory Animal Resources CoLSNRC (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DCGoogle Scholar
  9. 9.
    Keydar I, Chen L, Karby S, Weiss FR, Delarea J, Radu M, Chaitcik S, Brenner HJ (1979) Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer 15:659–670PubMedGoogle Scholar
  10. 10.
    Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A, Weinberg RA (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101:4966–4971PubMedCrossRefGoogle Scholar
  11. 11.
    Lacey JV Jr, Devesa SS, Brinton LA (2002) Recent trends in breast cancer incidence and mortality. Environ Mol Mutagen 39:82–88PubMedCrossRefGoogle Scholar
  12. 12.
    Lanari C, Kordon E, Molinolo A, Pasqualini CD, Charreau EH (1989) Mammary adenocarcinomas induced by medroxyprogesterone acetate: hormone dependence and EGF receptors of BALB/c in vivo sublines. Int J Cancer 43:845–850PubMedCrossRefGoogle Scholar
  13. 13.
    Liang TJ, Reid AE, Xavier R, Cardiff RD, Wang TC (1996) Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J Clin Invest 97:2872–2877PubMedCrossRefGoogle Scholar
  14. 14.
    Medina D, Kittrell FS, Shepard A, Contreras A, Rosen JM, Lydon J (2003) Hormone dependence in premalignant mammary progression. Cancer Res 63:1067–1072PubMedGoogle Scholar
  15. 15.
    Ménard S, Aiello P, Tagliabue E, Rumio C, Lollini PL, Colnaghi MI, Balsari A (2000) Tamoxifen chemoprevention of a hormone-independent tumor in proto-neu transgenic model. Cancer Res 60:273–275PubMedGoogle Scholar
  16. 16.
    Nandi S, Guzman RC, Yang J (1995) Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying hypothesis. Proc Natl Acad Sci USA 92:3650–3657PubMedCrossRefGoogle Scholar
  17. 17.
    Riggins RB, Schrecengost RS, Guerrero MS, Bouton AH (2007) Pathways to tamoxifen resistance. Cancer Lett 256:1–24PubMedCrossRefGoogle Scholar
  18. 18.
    Shyamala G, Chou YC, Louie SG, Guzman RC, Smith GH, Nandi S (2002) Cellular expression of estrogen and progesterone receptors in mammary glands: regulation by hormones, development and aging. J Steroid Biochem Mol Biol 80:137–148PubMedCrossRefGoogle Scholar
  19. 19.
    Soule HD, Vazguez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416PubMedGoogle Scholar
  20. 20.
    Valdes EK, Feldman SM, Boolbol SK (2007) Papillary lesions: a review of the literature. Ann Surg Oncol 14:1009–1013PubMedCrossRefGoogle Scholar
  21. 21.
    Watson CS, Medina D, Clark JH (1977) Estrogen receptor characterization in a transplantable mouse mammary tumor. Cancer Res 37:33–44Google Scholar
  22. 22.
    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 receptor expression during tumor progression. Cancer Res 60:6901–6910PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Marina Simian
    • 1
    • 2
  • Teresita Manzur
    • 1
    • 3
  • Vanina Rodriguez
    • 1
  • Elisa Bal de Kier Joffé
    • 1
    • 2
  • Slobodanka Klein
    • 1
  1. 1.Research Area, Institute of Oncology “Angel H. Roffo”University of Buenos AiresBuenos AiresArgentina
  2. 2.Consejo Nacional de Investigaciones Científicas y TécnicasBuenos AiresArgentina
  3. 3.Centro de Investigación en Reproducción Humana y ExperimentalInstituto Universitario CEMICBuenos AiresArgentina

Personalised recommendations