Display options
Cite
Bialesova L, Xu L, Gustafsson JÅ, et al. Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α. Oncotarget. 2017;8(44):76622-76633doi: 10.18632/oncotarget.20635.
Bialesova, L., Xu, L., Gustafsson, J. �. �., Haldosen, L. A., Zhao, C., & Dahlman-Wright, K. (2017). Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α. Oncotarget, 8(44), 76622-76633. https://doi.org/10.18632/oncotarget.20635
Bialesova, Lucia, et al. "Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α." Oncotarget vol. 8,44 (2017): 76622-76633. doi: https://doi.org/10.18632/oncotarget.20635
Bialesova L, Xu L, Gustafsson JÅ, Haldosen LA, Zhao C, Dahlman-Wright K. Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α. Oncotarget. 2017 Sep 04;8(44):76622-76633. doi: 10.18632/oncotarget.20635. eCollection 2017 Sep 29. PMID: 29100336; PMCID: PMC5652730.
Copy Download .nbib Format: NLM
Share it on

Oncotarget. 2017 Sep 04;8(44):76622-76633. doi: 10.18632/oncotarget.20635. eCollection 2017 Sep 29.

Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α.

Oncotarget

Lucia Bialesova, Li Xu, Jan-Åke Gustafsson, Lars-Arne Haldosen, Chunyan Zhao, Karin Dahlman-Wright

Affiliations

  1. Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge S-141 83, Sweden.
  2. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056, USA.

PMID: 29100336 PMCID: PMC5652730 DOI: 10.18632/oncotarget.20635

Abstract

The two estrogen receptor (ER) subtypes, ERα and ERβ, belong to the nuclear receptor superfamily. The human ERβ variant ERβ2 is proposed to be expressed at higher levels than ERβ1 in many breast tumors and it has been suggested that ERβ2, in contrast to ERβ1, is associated with aggressive phenotypes of various cancers. However, the role of endogenous ERβ2 in breast cancer cells remains elusive. In this study, we identified that triple negative breast cancer (TNBC) cell lines express endogenous ERβ2, but not ERα or ERβ1. This allows novel studies of endogenous ERβ2 functions independent of ERα and ERβ1. We show that overexpression of ERβ2 in TNBC cells increased whereas knockdown of endogenous ERβ2 decreased cell proliferation and cell invasion. To elucidate the molecular mechanism responsible for these cellular phenotypes, we assayed ERβ2 dependent global gene expression profiles. We show that ERβ2 decreases prolyl hydroxylase 3 (PHD3) gene expression and further show that this is associated with increased hypoxia inducible factor 1α (HIF-1α) protein levels, thus providing a possible mechanism for the invasive phenotype. These results are further supported by analysing the expression of ERβ2 and PHD3 in breast tumor samples where a negative correlation between ERβ2 and PHD3 expression was observed. Together, we demonstrate that ERβ2 has an important role in enhancing cell proliferation and invasion, beyond modulation of ERβ and ERβ1 signalling which might contribute to the invasive characteristics of TNBC. The invasive phenotype could potentially be mediated through transcriptional repression of PHD3 and increased HIF-1α protein levels.

Keywords: ERβ isoform; ERβ2; PHD3; breast cancer; gene expression profile

Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

References

  1. Nat Commun. 2017 Jun 15;8:15840 - PubMed
  2. Mol Cell Endocrinol. 2014 Jan 25;382(1):665-72 - PubMed
  3. Biochem Biophys Res Commun. 2013 Nov 1;440(4):652-7 - PubMed
  4. Br J Cancer. 2010 Nov 9;103(10):1571-9 - PubMed
  5. Cancer Chemother Pharmacol. 2005 Nov;56 Suppl 1:21-6 - PubMed
  6. Neurol Sci. 2013 Mar;34(3):365-71 - PubMed
  7. Breast Cancer Res Treat. 2012 May;133(1):179-88 - PubMed
  8. Biol Reprod. 2012 Aug 30;87(2):47 - PubMed
  9. J Cell Physiol. 2012 Feb;227(2):514-24 - PubMed
  10. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925-30 - PubMed
  11. J Clin Oncol. 2003 Oct 1;21(19):3580-7 - PubMed
  12. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13221-6 - PubMed
  13. Breast Cancer Res Treat. 2011 Feb;125(3):627-36 - PubMed
  14. Oncotarget. 2016 Nov 22;7(47):77793-77806 - PubMed
  15. FEBS Lett. 2012 Nov 2;586(21):3831-9 - PubMed
  16. J Cancer Res Clin Oncol. 2014 Mar;140(3):503-13 - PubMed
  17. J Steroid Biochem Mol Biol. 1998 Nov;67(3):233-40 - PubMed
  18. Cancer Res. 2007 Apr 15;67(8):3955-62 - PubMed
  19. J Hematol Oncol. 2013 Jan 05;6:3 - PubMed
  20. J Cell Biochem. 2010 May;110(1):52-61 - PubMed
  21. Am J Clin Oncol. 2010 Dec;33(6):637-45 - PubMed
  22. APMIS. 2008 Oct;116(10):923-30 - PubMed
  23. Int J Surg. 2015 Feb;14:17-22 - PubMed
  24. J Steroid Biochem. 1986 Jan;24(1):77-83 - PubMed
  25. Breast Cancer Res. 2011 Aug 12;13(4):215 - PubMed
  26. PLoS One. 2013 Dec 20;8(12):e84127 - PubMed
  27. Clin Cancer Res. 2004 Sep 1;10(17):5769-76 - PubMed
  28. J Zhejiang Univ Sci B. 2015 Jan;16(1):32-43 - PubMed
  29. Clin Cancer Res. 2004 Apr 1;10(7):2421-8 - PubMed
  30. PLoS One. 2013 Nov 28;8(11):e81347 - PubMed
  31. Mol Endocrinol. 2012 Dec;26(12 ):1991-2003 - PubMed
  32. PLoS One. 2013 Dec 18;8(12):e83021 - PubMed
  33. J Natl Cancer Inst. 2004 Jun 16;96(12):946-56 - PubMed
  34. Biochem Pharmacol. 2000 Jan 1;59(1):47-53 - PubMed
  35. Clin Chem. 2014 Mar;60(3):451-4 - PubMed
  36. Carcinogenesis. 2012 Sep;33(9):1684-91 - PubMed
  37. Nat Rev Clin Oncol. 2016 Nov;13(11):674-690 - PubMed
  38. Mol Pharmacol. 2006 Nov;70(5):1469-80 - PubMed
  39. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1566-71 - PubMed
  40. Oncogene. 2013 May 9;32(19):2390-402 - PubMed
  41. Nucleic Acids Res. 1998 Aug 1;26(15):3505-12 - PubMed

Publication Types