Comparison of the Effects of the Selective Estrogen Receptor Modulators Ospemifene, Raloxifene, and Tamoxifen on Breast Tissue in Ex Vivo Culture

  • Natalija Eigeliene
  • Risto Erkkola
  • Pirkko Härkönen
Part of the Methods in Molecular Biology book series (MIMB, volume 1366)

Abstract

Explant tissue culture provides a model for studying the direct effects of steroid hormones, their analogs, and novel hormonally active compounds on normal freshly isolated human breast tissues (HBTs). For this purpose, pre- and postmenopausal HBTs can be maintained in this culture system. The results demonstrate that the morphological integrity of HBT explants can be maintained in tissue culture up to 2 weeks and expression of differentiation markers, steroid hormone receptors, proliferation and apoptosis ratios can be evaluated as a response to hormonal stimulation. This chapter describes an ex vivo culture model that we have applied to study the effects of various hormonally active substances, including 17β-estradiol and selective estrogen receptor modulators (SERMs), on normal human breast tissues.

Key words

Human breast tissue Explant tissue culture Estradiol Estrogenreceptoralpha SERMs 

Notes

Acknowledgments

This work was supported by the Turku University Hospital, the Academy of Finland, and the Sigfrid Jusélius Foundation.

References

  1. 1.
    Eigeliene N, Harkonen P, Erkkola R (2006) Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures. BMC Cancer 6:246CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Burdall SE, Hanby AM, Lansdown MR, Speirs V (2003) Breast cancer cell lines: friend or foe? Breast Cancer Res 5(2):89–95CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zhuang YH, Saaristo R, Ylikomi T (2003) An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors. Cell Tissue Res 311(2):217–226PubMedGoogle Scholar
  4. 4.
    Stute P, Wood CE, Kaplan JR, Cline JM (2004) Cyclic changes in the mammary gland of cynomolgus macaques. Fertil Steril 82(Suppl 3):1160–1170CrossRefPubMedGoogle Scholar
  5. 5.
    Isaksson E, Wang H, Sahlin L, von Schoultz B, Cline JM, von Schoultz E (2003) Effects of long-term HRT and tamoxifen on the expression of progesterone receptors A and B in breast tissue from surgically postmenopausal cynomolgus macaques. Breast Cancer Res Treat 79(2):233–239CrossRefPubMedGoogle Scholar
  6. 6.
    Cline JM, Soderqvist G, von Schoultz E, Skoog L, von Schoultz B (1998) Effects of conjugated estrogens, medroxyprogesterone acetate, and tamoxifen on the mammary glands of macaques. Breast Cancer Res Treat 48(3):221–229CrossRefPubMedGoogle Scholar
  7. 7.
    Parmar H, Cunha GR (2004) Epithelial–stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer 11(3):437–458CrossRefPubMedGoogle Scholar
  8. 8.
    Levine JF, Stockdale FE (1985) Cell-cell interactions promote mammary epithelial cell differentiation. J Cell Biol 100(5):1415–1422CrossRefPubMedGoogle Scholar
  9. 9.
    Ronnov-Jessen L, Petersen OW, Bissell MJ (1996) Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev 76(1):69–125CrossRefPubMedGoogle Scholar
  10. 10.
    Dean JL, McClendon AK, Hickey TE et al (2012) Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors. Cell Cycle 11(14):2756–2761CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Eigeliene N, Harkonen P, Erkkola R (2008) Effects of estradiol and medroxyprogesterone acetate on expression of the cell cycle proteins cyclin D1, p21 and p27 in cultured human breast tissues. Cell Cycle 7(1):71–80CrossRefPubMedGoogle Scholar
  12. 12.
    Eigeliene N, Elo T, Linhala M, Hurme S, Erkkola R, Harkonen P (2012) Androgens inhibit the stimulatory action of 17beta-estradiol on normal human breast tissue in explant cultures. J Clin Endocrinol Metab 97(7):E1116–E1127CrossRefPubMedGoogle Scholar
  13. 13.
    Trowell OA (1959) The culture of mature organs in a synthetic medium. Exp Cell Res 16(1):118–147.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Natalija Eigeliene
    • 1
  • Risto Erkkola
    • 2
  • Pirkko Härkönen
    • 1
  1. 1.Department of Cell Biology and Anatomy, Institute of BiomedicineUniversity of TurkuTurkuFinland
  2. 2.Department of Obstetrics and GynecologyTurku University Central HospitalTurkuFinland

Personalised recommendations