Breast Cancer Research and Treatment

, Volume 80, Issue 1, pp 79–85 | Cite as

Expression of Estrogen Receptor-β in Normal Mammary and Tumor Tissues: is it Protective in Breast Carcinogenesis?

  • Byeong-Woo Park
  • Ki-Suk Kim
  • Min-Kyu Heo
  • Seung-Sang Ko
  • Kyong Sik Lee
  • Soon Won Hong
  • Woo-Ick Yang
  • Joo-Hang Kim
  • Gwi Eon Kim


Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-β (ERβ) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERβ in BC development and progression. ERβ expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERβ mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERβ mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERβ expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERβ expression. Collectively, ERβ mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

breast cancer carcinogenesis estrogen receptor-β in situ hybridization prognosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    George FW, Wilson FD: Sex determination and differentiation. In: Knobil E, Neill JD (eds) The Physiology of Reproduction. Raven Press, New York, 1988, pp. 3-26Google Scholar
  2. 2.
    Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P: Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320: 134-139, 1986Google Scholar
  3. 3.
    Greene GL, Gilna P, Waterfield M, baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science 231: 1150-1154, 1986Google Scholar
  4. 4.
    Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA: Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93: 5925-5930, 1996Google Scholar
  5. 5.
    Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V: Cloning, chromosomal localization and functional analysis of the murine estrogen receptor-β. Mol Endocrinol 11: 353-365, 1997Google Scholar
  6. 6.
    Mosselman S, Polman J, Dijkema R: ER-β: identification and characterization of a novel human estrogen receptor. FEBS Lett 392: 49-53, 1996Google Scholar
  7. 7.
    Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjold M, Gustafsson JA: Human estrogen receptorβ-gene structure, chromosomal localization and expression pattern. J Clin Endocrinol Metabiol 82: 4258-4265, 1997Google Scholar
  8. 8.
    Taylor AH, Al-Azzawi F: Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 24: 145-155, 2000Google Scholar
  9. 9.
    Hall JM, McDonnell DP: The estrogen receptor β-isoform (ERα) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140: 5566-5578, 1999Google Scholar
  10. 10.
    Korach KS: Insights from the study of animals lacking functional estrogen receptor. Science 266: 1524-1527, 1994Google Scholar
  11. 11.
    Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O: Generation and reproductive phenotypes of mice lacking estrogen receptor α. Proc Natl Acad Sci USA 95: 15677-15682, 1998Google Scholar
  12. 12.
    Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H: Decreased expression of estrogen receptor α protein in proliferative preinvasive mammary tumors. Cancer Res 61: 2537-2541, 2001Google Scholar
  13. 13.
    Leygue E, Dotzlaw H, Watson PH, Murphy LC: Altered estrogen receptor α and α messenger RNA expression during human breast tumorigenesis. Cancer Res 58: 3197-3201, 1998Google Scholar
  14. 14.
    Jarvinen TA, Pelto-Huikko M, Holli K, Isola J: Estrogen receptor α is coexpressed with ERα and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol 156: 29-35, 2000Google Scholar
  15. 15.
    Hu YF, Lau KM, Ho SM, Russo J: Increased expression of estrogen receptor beta in chemically transformed human breast epithelial cells. Int J Oncol 12: 1225-1228, 1998Google Scholar
  16. 16.
    Dotzlaw H, Leygue E, Watson PH, Murphy LC: Expression of estrogen receptor beta in human breast tumors. J Clin Endocrinol Metabiol 82: 2371-2374, 1997Google Scholar
  17. 17.
    Mann S, Laucirica R, Carlson N, Younes PS, Ali N, Younes A, Li Y, Younes M: Estrogen receptor beta expression in invasive breast cancer. Human Pathol 32: 113-118, 2001Google Scholar
  18. 18.
    Speirs V, Parkes AT, Kerin MJ, Walton DS, Carleton PJ, Fox JN, Atkin SL: Coexpression of estrogen receptor α and α: poor prognostic factors in human breast cancer? Cancer Res 59: 525-528, 1999Google Scholar
  19. 19.
    Speirs V, Kerin MJ: Prognostic significance of oestrogen receptor beta in breast cancer. Br J Surg 87: 405-409, 2000Google Scholar
  20. 20.
    Speirs V, Adams IP, Walton DS, Atkin SL: Identification of wild-type and exon 5 deletion variants of estrogen receptor α in normal human mammary gland. J Clin Endocrinol Metabiol 85: 1601-1605, 2000Google Scholar
  21. 21.
    Skliris GP, Carder PJ, Lansdown MRJ, Speirs V: Immunohistochemical detection of ERα in breast cancer: towards more detailed receptor profiling? Br J Cancer 84: 1095-1098, 2001Google Scholar
  22. 22.
    Gustafsson JA, Warner M: Estrogen receptor α in the breast: role in estrogen responsiveness and development of breast cancer. J Steroid Biochem Mol Biol 74: 245-248, 2000Google Scholar
  23. 23.
    Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lupu R: Expression of estrogen receptor α messenger RNA variant in breast cancer. Cancer Res 58: 210-214, 1998Google Scholar
  24. 24.
    Speirs V, Malone C, Walton DS, Kerin MJ, Atkin SL: Increased expression of estrogen receptor α mRNA in tamoxifen-resistant breast cancer patients. Cancer Res 59: 5421-5424, 1999Google Scholar
  25. 25.
    Dotzlaw H, Leygue E, Watson PH, Murphy LC: Estrogen receptor-α messenger RNA expression in human breast tumor biopsies: relationship to steroid receptor status and regulation by progestins. Cancer Res 59: 529-532, 1999Google Scholar
  26. 26.
    Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: Molecular cloning and characterization of human estrogen receptor αcx: a potential inhibitor of estrogen action in human. Nucl Acids Res 26: 3505-3512, 1998Google Scholar
  27. 27.
    Palmieri C, Cheng GJ, Saji S, Zealda-Hedman M, Warri A, Weihua Z, Noorden SV, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA: Estrogen receptor beta in breast cancer. Endocr-Relat Cancer 9: 1-13, 2002Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Byeong-Woo Park
    • 1
    • 3
  • Ki-Suk Kim
  • Min-Kyu Heo
  • Seung-Sang Ko
    • 1
  • Kyong Sik Lee
    • 1
  • Soon Won Hong
    • 2
  • Woo-Ick Yang
    • 2
  • Joo-Hang Kim
    • 3
  • Gwi Eon Kim
    • 3
  1. 1.Department of SurgeryYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea
  3. 3.Brain Korea 21 ProjectYonsei University College of MedicineSeoulSouth Korea

Personalised recommendations