Skip to main content

Advertisement

SpringerLink
Log in

Estrogen receptor-β regulates psoriasin (S100A7) in human breast cancer

  • Original Paper
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We have previously observed a paradoxical relationship of the psoriasin/S100A7 gene with estrogen response in-vitro in ERα positive cells but its association with ERα negative status in-vivo raising the possibility that S100A7 might be regulated by ERβ in breast cancer. Using doxycycline-inducible ERβ and ERα expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is ERβ regulated was investigated To explore the relationship between psoriasin/S100A7 and ERβ expression in-vivo, we also assessed a cohort of 233 ERα negative breast tumors using tissue microarrays and immunohistochemistry. Psoriasin/S100A7 was increased by 17β-estradiol (E2) following ERβ induction, in several clones of ERβ over-expressing but not in the original MCF-7 cells, nor clones over-expressing ERα. The effect of E2 on psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with a selective ERα antagonist. An ERβ selective-agonist but not an ERα selective-agonist, induced psoriasin/S100A7. This induction still occurred after stable down-regulation of ERα using siRNA in ERβ inducible cells. E2 increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this effect. A relationship between ERβ and psoriasin/S100A7 was observed in the p53 immunohistochemically negative subset of invasive breast tumors in-vivo (r = 0.225, p = 0.046, n = 79). In conclusion we demonstrate that E2 induction of psoriasin/S100A7 can be specifically regulated through ERβ in-vitro and associated with ERβ in-vivo. These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERβ activity and could be useful to guide future therapies targeting ERβ in certain phenotypic subsets of breast cancers in-vivo.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ali S, Coombes R (2002) Endocrine-responsive breast cancer and strategies for combating resistance. Nature Rev 2:101–112

    Article  Google Scholar 

  2. Lippman M, Bolan G (1975) Oestrogen responsive human breast cancer in long term tissue culture. Nature 256(5518):592–593

    Article  PubMed  CAS  Google Scholar 

  3. Horwitz K, Koseki Y, McGuire W (1978) Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen. Endocrinology 103:1742–1751

    Article  PubMed  CAS  Google Scholar 

  4. Bardou V, Arpino G, Elledge R, Osborne C, Clark G (2003) Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 21:1973–1979

    Article  PubMed  CAS  Google Scholar 

  5. Holland P, Knox W, Potten C, Howell A, Anderson E, Baildam A, Bundred N (1997) Assessment of hormone dependence of comedo ductal carcinoma in situ of the breast. J Natl Cancer Inst 89(14):1059–1065

    Article  PubMed  CAS  Google Scholar 

  6. Lapidus R, Nass S, Davidson N (1998) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia 3:85–94

    Article  PubMed  CAS  Google Scholar 

  7. Leygue E, Dotzlaw H, Watson P, Murphy L (1998) Altered estrogen receptor alpha and beta mRNA expression during human breast tumorigenesis. Cancer Res 58:3197–3201

    PubMed  CAS  Google Scholar 

  8. Jarvinen T, Pelto-Huikko M, Holli K, Isola J (2000) Estrogen receptor beta is coexpressed with ER alpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol 156:29–35

    PubMed  CAS  Google Scholar 

  9. Forster C, Makela S, Warri A, Kietz S, Becker D, Hultenby K, Warner M, Gustafsson J (2002) Involvement of estrogen receptor b in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A 99(24):15578–15583

    Article  PubMed  CAS  Google Scholar 

  10. Hall J, McDonnell D (1999) The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140:5566–5578

    Article  PubMed  CAS  Google Scholar 

  11. Weihua Z, Saji S, Makinen S, Cheng G, Jensen E, Warner M, Gustaffson J-A (2000) Estrogen receptor (ER) b, a modulator of ERa in the uterus. Proc Natl Acad Sci 97(11):5936–5941

    Article  PubMed  CAS  Google Scholar 

  12. Roger P, Sahla M, Makela S, Gustafsson JA, Baldet P, Rochefort H (2001) Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors. Cancer Res 61:2537–2541

    PubMed  CAS  Google Scholar 

  13. Speirs V (2002) Oestrogen receptor beta in breast cancer: good, bad or still too early to tell? J Pathol 197(2):143–147

    Article  PubMed  CAS  Google Scholar 

  14. Speirs V, Parkes A, Kerin M, Walton D, Carleton P, Fox J, Atkin S (1999) Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer? Cancer Res 59(3):525–528

    PubMed  CAS  Google Scholar 

  15. Skliris G, Carder P, Lansdown M, Speirs V (2001) Immunochemical detection of Erbeta in breast cancer: towards more detailed receptor profiling? Br J Cancer 84:1095–1098

    Article  PubMed  CAS  Google Scholar 

  16. Mann S, Laucirica R, Carlson N, Younes P, Ali N, Younes A, Li Y, Younes M (2001) estrogen receptor beta expression in invasive breast cancer. Hum Pathol 32:113–118

    Article  PubMed  CAS  Google Scholar 

  17. Murphy L, Leygue E, Niu Y, Snell L, Ho S-M, Watson P (2002) Relationship of coregulator and estrogen receptor isoform expression to de novo tamoxifen resistance in human breast cancer. British J Cancer 87:1411–1416

    Article  CAS  Google Scholar 

  18. Fleming F, Hill A, McDermott E, O’Higgins N, Young L (2004) Differential recruitment of coregulator proteins steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors to the estrogen receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in human breast cancer. J Clin Endocrinol Metab 89(1):375–383

    Article  PubMed  CAS  Google Scholar 

  19. Esslimani-Sahla M, Simony-Lafontaine J, Kramar A, Lavaill R, Mollevi C, Warner M, Gustafsson J-A, Rochefort H (2004) Estrogen receptor beta (ERbeta) level but not its ERbeta-cx variant helps to predict tamoxifen resistance in breast cancer. Clin Cancer Res 10:5769–5776

    Article  PubMed  CAS  Google Scholar 

  20. Hopp T, Weiss H, Parra I, Cui Y, Osborne C, Fuqua S (2004) Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer. Clin Cancer Res 10(22):7490–7499

    Article  PubMed  CAS  Google Scholar 

  21. Iwase H, Zhang Z, Omoto Y, Sugiura H, Yamashita H, Toyama T, Iwata H, Kobayashi S (2003) Clinical significance of the expression of estrogen receptors alpha and beta for endocrine therapy of breast cancer. Cancer Chemother Pharmacol 52 Suppl (1):S34–38

    Article  PubMed  CAS  Google Scholar 

  22. Myers E, Fleming F, Crotty T, Kelly G, McDermott E, O’Higgins N, Hill A, Young L (2004) Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine resistant breast cancer. Br J Cancer 91:1687–1693

    PubMed  CAS  Google Scholar 

  23. Nakopoulou L, Panayotopoulou AL, Giannopoulou I, Givalos N, Markaki S, Keramopoulos A (2004) The favourable prognostic value of oestrogen receptor beta immunohistochemical expression in breast cancer. J Clin Pathol 57(5):523–528

    Article  PubMed  CAS  Google Scholar 

  24. Omoto Y, Inoue S, Ogawa S, Toyama T, Yamashita H, Muramatsu M, Kobayashi S, Iwase H (2001) Clinical value of the wild-type estrogen receptor beta expression in breast cancer. Cancer Lett 163(2):207–212

    Article  PubMed  CAS  Google Scholar 

  25. O’Neill P, Davies M, Shaaban A, Innes H, Torevell A, Sibson D, Foster C (2004) Wild-type oestrogen receptor beta (ERbeta1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers. Br J Cancer 91(9):1694–1702

    PubMed  CAS  Google Scholar 

  26. Murphy L, Cherlet T, Lewis A, Banu Y, Watson P (2003) New insights into estogen receptor function in human breast cancer. Ann Med 35(8):614–631

    Article  PubMed  CAS  Google Scholar 

  27. Osborne C (1998) Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat 51:227–238

    Article  PubMed  CAS  Google Scholar 

  28. Kraichely D, Sun J, Katzenellenbogen J, Katzenellenbogen B (2000) Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-alpha and estrogen receptor-beta: correlations with biological character and distinct differences among SRC coactivator family members. Endocrinol 141(10):3534–3545

    Article  CAS  Google Scholar 

  29. Murphy L, Peng B, Lewis A, Davie J, Leygue E, Kemp A, Ung K, Vendetti M, Shiu R (2005) Inducible upregulation of oestrogen receptor-beta1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells. J Mol Endocrinol 34(2):553–566

    Article  PubMed  CAS  Google Scholar 

  30. Emberley E, Niu Y, Leygue E, Tomes L, Gietz R, Murphy L, Watson P (2003) Psoriasin interacts with Jab1 and influences breast cancer progression. Cancer Res 63:1954–1961

    PubMed  CAS  Google Scholar 

  31. Leygue E, Snell L, Hiller H, Dotzlaw H, Hole K, Murphy L, Watson P (1996): Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma. Erratum in: Cancer Res 1997;57:793. Cancer Res 56:4606–4609

  32. Serrano M, Lin A, McCurrach M, Beach D, Lowe S (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602

    Article  PubMed  CAS  Google Scholar 

  33. Watson P, Snell L, Parisien M (1996) The NCIC-Manitoba Breast Tumor Bank: a resource for applied cancer research. CMAJ 155:281–283

    PubMed  CAS  Google Scholar 

  34. Al-haddad S, Zhang Z, Leygue E, Snell L, Huang A, Niu Y, Hiller-Hitchcock T, Hole K, Murphy L, Watson P (1999) Psoriasin (S100A7) expression and invasive breast cancer. Am J Pathol 155:2057–2066

    PubMed  CAS  Google Scholar 

  35. Emberley E, Niu Y, Njue C, Kliewer E, Murphy L, Watson P (2003) Psoriasin (S100A7) expression is associated with poor outcome in estrogen receptor-negative invasive breast cancer. Clin Cancer Res 9:2627–2631

    PubMed  CAS  Google Scholar 

  36. Emberley E, Niu Y, Curtis L, Troup S, Mandal S, Myers J, Gibson S, Murphy L, Watson P (2005) The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer.soriasin (S100A7) stimulates pro-survival pathways through activation of Jab1 in breast cancer. Cancer Res 65(13):5696–5702

    Article  PubMed  CAS  Google Scholar 

  37. Skliris G, Munot K, Bell S, Carder P, lane S, Horgan K, Lansdown M, Parkes A, Hanby A, Markham A et al (2003) Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyltransferase inhibitors in a cell line model. J Pathol 201:213–220

    Article  PubMed  CAS  Google Scholar 

  38. Allred D, Clark G, Elledge R, Fuqua S, Brown R, Chamness G, Osborne O, McGuire W (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85(3):200–206

    Article  PubMed  CAS  Google Scholar 

  39. Moog-Lutz C, Bouillet P, Regnier C, Tomasetto C, Mattei M, Chenard M, Anglard P, Rio M, Basset P (1995) Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22. Int J Cancer 63:297–303

    Article  PubMed  CAS  Google Scholar 

  40. Venditti M, Iwasiow B, Orr F, Shiu R (2002) C-myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells. Int J Cancer 99(1):35–42

    Article  PubMed  CAS  Google Scholar 

  41. Sun J, Huang Y, Harrington W, Sheng S, Katzenellenbogen J, Katzenellenbogen B (2002) Antagonists selective for estrogen receptor alpha. Endocrinology 143(3):941–947

    Article  PubMed  CAS  Google Scholar 

  42. Watson P, Chia S, Wykoff C, Han C, Leek R, Sly W, Gatter K, Ratcliffe P, Harris A (2003) Carbonic Anhydrase XII is a marker of good prognosis in Invasive Breast Carcinoma. Br J Cancer 88:1065–1070

    Article  PubMed  CAS  Google Scholar 

  43. Concin N, Zeillinger C, Tong D, Stimpfl M, Konig M, Printz D, Stonek F, Schneeberger C, Hefler L, Kainz C et al (2003) Comparison of p53 mutational status with mRNA and protein expression in a panel of 24 human breast carcinoma cell lines. Breast Cancer Res Treat 79(1):37–46

    Article  PubMed  CAS  Google Scholar 

  44. Montano M, Jaiswal A, Katzenellenbogen B (1998) Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. J Biol Chem 273(39):25443–25449

    Article  PubMed  CAS  Google Scholar 

  45. Lindberg M, Moverare S, Skrtic S, Gao H, Dahlman-Wright K, Gustafsson J, Ohlsson C (2003) Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a “ying yang” relationship between ERalpha and ERbeta in mice. Mol Endocrinol 17(2):203–208

    Article  PubMed  CAS  Google Scholar 

  46. Otsuki M, Gao H, Dahlman-Wright K, Ohlsson C, Eguchi N, Urade Y, Gustafsson J (2003) Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta. Mol Endocrinol 17(9):1844–1855

    Article  PubMed  CAS  Google Scholar 

  47. Patisaul H, Scordalakes E, Young L, Rissman E (2003) Oxytocin, but not oxytocin receptor, is rRegulated by oestrogen receptor beta in the female mouse hypothalamus. J Neuroendocrinol 15(8):787–793

    Article  PubMed  CAS  Google Scholar 

  48. Cao L, Bu R, Oakley J, Kalla S, Blair H (2003) Estrogen receptor-beta modulates synthesis of bone matrix proteins in human osteoblast-like MG63 cells. J Cell Biochem 89(1):152–164

    Article  PubMed  CAS  Google Scholar 

  49. Monroa D, Getz B, Johnsen S, Riggs BL, Khosla S, Spelsberg T (2003) Estrogen rceptor isoform specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ERalpha or ER beta. J Cell Biochem 90:315–326

    Article  CAS  Google Scholar 

  50. An J, Ribeiro R, Webb P, Gustafsson J, Kushner P, Baxter J, Leitman D (1999) Estradiol repression of tumor necrosis factor-alpha transcription requires estrogen receptor activation function-2 and is enhanced by coactivators. Proc Natl Acad Sci U S A 96(26):15161–15166

    Article  PubMed  CAS  Google Scholar 

  51. Jensen E, Cheng G, Palmieri C, Saji S, Makela S, Noorden Sv, Wahlstrom T, Warner M, Coombes R, Gustafsson J-A (2001) Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc Natl Acad Sci U S A 98:15197–15202

    Article  PubMed  CAS  Google Scholar 

  52. Lewandowski S, Thiery J, Jalil A, Leclercq G, Szczylik C, Chouaib S (2005) Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity. Oncogene 24(30):4789–4798

    Article  PubMed  CAS  Google Scholar 

  53. Nuzzo SD, Sylva-Steenland R, Koomen C, Rie Md, Das P, Bos J, Teunissen M (2000) Exposure to UVB induces accumulation of LFA-1+ T cells and enhanced expression of the chemokine psoriasin in normal human skin. Photochem Photobiol 72(3):374–382

    Article  PubMed  Google Scholar 

  54. Enerback C, Porter D, Seth P, Sgroi D, Gaudet J, Weremowicz S, Morton C, Schnitt S, Pitts R, Stampl J et al (2002) Psoriasin expression in mammary epithelial cells in vitro and in vivo. Cancer Res 62:43–47

    PubMed  CAS  Google Scholar 

  55. Paruthiyil S, Parmar H, Kerekatte V, Cunha G, Firestone G, Leitman D (2004) Estrogen receptor b inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Res 64:423–428

    Article  PubMed  CAS  Google Scholar 

  56. Qiu Y, Waters C, Lewis A, Langmann M, Eggo M (2002) Oestrogen induced apoptosis in colonocytes expressing oestrogen receptor beta. J Endocrinol 174:369–377

    Article  PubMed  CAS  Google Scholar 

  57. Liu G, Schwartz J, Brooks S (2000) Estrogen receptor protects p53 from deactivation by human double minute-2. Cancer Res 60:1810–1814

    PubMed  CAS  Google Scholar 

  58. Kennedy R, Gorski J, Quinn J, Stewart G, James C, Moore S, Mulligan K, Emberley E, Lioe T, Morrison P et al (2005) BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene. Cancer Res 65:10265–10272

    Article  PubMed  CAS  Google Scholar 

  59. Ho J, Ma W, Mao D, Benchimol S (2005) p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol 25:7423–7431

    Article  PubMed  CAS  Google Scholar 

  60. Foulkes W, Brunet J, Stefansson I, Straume O, Chappuis P, Begin L, Hamel N, Goffin J, Wong N, Trudel M et al (2004) The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 64(3):830–835

    Article  PubMed  CAS  Google Scholar 

  61. Grigorian M, Andresen S, Tulchinsky E, Kriajevska M, Carlberg C, Kruse C, Cohn M, Ambartsumian N, Christensen A, Selivanova G et al (2001) Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein: functional consequences of their interaction. J Biol Chem 276(25):22699–22708

    Article  PubMed  CAS  Google Scholar 

  62. Mueller A, Schafer B, Ferrari S, Weibel M, Makek M, Hochli M, Heizmann C (2005) The calcium-binding protein S100A2 interacts with p53 and modulates its transcriptional activity. J Biol Chem 280(32):29186–29193

    Article  PubMed  CAS  Google Scholar 

  63. Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W (2001) COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. Embo J 20(7):1630–1639

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

G.P.S is funded by a postdoctoral fellowship from the Manitoba Health Research Council (MHRC) and previously from the CancerCare Manitoba Foundation (CCMF). AL was funded by a Guardian Angel/CCMF Studentship. EE was funded by a National Cancer Institute of Canada (NCIC) Terry Fox Research Studentship. WW is funded by a CCMF postdoctoral fellowship. J.R.D holds a Canada Research Chair. The research is supported by Canadian Institutes of Health Research (CIHR), Canadian Breast Cancer Research Alliance (CBCRA), CCMF and USAMRMC operating grants. We acknowledge the strong support of the CCMF for our facilities at MICB. The authors have no known conflicts of interests either financial or personal between themselves and others that might bias the work.

Author information

Authors and Affiliations

  1. Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, Canada

    George P. Skliris, Anthony Lewis, Ethan Emberley, Baocheng Peng, James R. Davie, Peter H. Watson & Leigh C. Murphy

  2. Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Ave, R3E0V9, Winnipeg, MB, Canada

    George P. Skliris, Anthony Lewis, Baocheng Peng, Wineeta K. Weebadda, Angela Kemp, James R. Davie, Robert P. C. Shiu, Peter H. Watson & Leigh C. Murphy

  3. Department of Physiology, University of Manitoba, Winnipeg, Canada

    Robert P. C. Shiu

  4. Department of Pathology, University of Manitoba, Winnipeg, Canada

    Ethan Emberley & Peter H. Watson

Authors
  1. George P. Skliris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ethan Emberley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baocheng Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wineeta K. Weebadda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angela Kemp
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James R. Davie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert P. C. Shiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter H. Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leigh C. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leigh C. Murphy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Skliris, G.P., Lewis, A., Emberley, E. et al. Estrogen receptor-β regulates psoriasin (S100A7) in human breast cancer. Breast Cancer Res Treat 104, 75–85 (2007). https://doi.org/10.1007/s10549-006-9390-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9390-x

Keywords

Search

Navigation