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Article

Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region

  • Authors:
    • Hakeemah Al-Nakhle
    • Laura Smith
    • Sandra M. Bell
    • Philip A. Burns
    • Michele Cummings
    • Andrew M. Hanby
    • Sally Lane
    • Marie D. Parker
    • Thomas A. Hughes
    • Valerie Speirs
  • View Affiliations / Copyright

    Affiliations: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds LS9 7TF, UK, St James's Institute of Oncology, St James's University Hospital, Leeds LS9 7TF, UK
  • Pages: 2039-2045
    |
    Published online on: September 25, 2013
       https://doi.org/10.3892/ijo.2013.2112
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Abstract

ERβ1 is often down-regulated in breast cancer compared to normal breast but mechanisms surrounding this are unclear. We examined whether loss of heterozygosity (LOH) or methylation at ERβ promoters (0N, 0K) and/or untranslated exon 0N were involved in ERβ down-regulation in breast cancer tissues and cell lines and if treatment with the de-methylating agent 5-aza-deoxycytidine and/or the histone deacetylase inhibitor Trichostatin A could influence expression in vitro. We found no evidence of correlation between LOH at 14q22-24 (genomic locus containing ERβ/ESR2), and ERβ1 expression in primary breast cancers. A negative correlation between ERβ1 mRNA expression and methylation status was observed for promoter 0N in BT-20, MDA-MB-453 and T47D cells. Promoter 0K was consistently unmethylated. In primary breast tumours, methylation of the untranslated exon 0N, downstream of promoter 0N, but not of promoter 0N itself, correlated with down-regulation of ERβ. In MDA-MB-453 cells, treatment with 5-aza-deoxycytidine was sufficient to induce ERβ1 expression from the 0N promoter while in BT-20 both agents were required. Examination of various sites on ESR2 highlighted epigenetic but not genetic regulation of ERβ1. In particular methylation adjacent to promoter 0N was a key regulatory event for ERβ1 silencing. A combination of de-methylating agents and histone deacetylase inhibitors fully restored ERβ1 expression which may offer a novel therapeutic angle for breast cancer management.
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Copy and paste a formatted citation
Spandidos Publications style
Al-Nakhle H, Smith L, Bell SM, Burns PA, Cummings M, Hanby AM, Lane S, Parker MD, Hughes TA, Speirs V, Speirs V, et al: Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region. Int J Oncol 43: 2039-2045, 2013.
APA
Al-Nakhle, H., Smith, L., Bell, S.M., Burns, P.A., Cummings, M., Hanby, A.M. ... Speirs, V. (2013). Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region. International Journal of Oncology, 43, 2039-2045. https://doi.org/10.3892/ijo.2013.2112
MLA
Al-Nakhle, H., Smith, L., Bell, S. M., Burns, P. A., Cummings, M., Hanby, A. M., Lane, S., Parker, M. D., Hughes, T. A., Speirs, V."Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region". International Journal of Oncology 43.6 (2013): 2039-2045.
Chicago
Al-Nakhle, H., Smith, L., Bell, S. M., Burns, P. A., Cummings, M., Hanby, A. M., Lane, S., Parker, M. D., Hughes, T. A., Speirs, V."Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region". International Journal of Oncology 43, no. 6 (2013): 2039-2045. https://doi.org/10.3892/ijo.2013.2112
Copy and paste a formatted citation
x
Spandidos Publications style
Al-Nakhle H, Smith L, Bell SM, Burns PA, Cummings M, Hanby AM, Lane S, Parker MD, Hughes TA, Speirs V, Speirs V, et al: Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region. Int J Oncol 43: 2039-2045, 2013.
APA
Al-Nakhle, H., Smith, L., Bell, S.M., Burns, P.A., Cummings, M., Hanby, A.M. ... Speirs, V. (2013). Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region. International Journal of Oncology, 43, 2039-2045. https://doi.org/10.3892/ijo.2013.2112
MLA
Al-Nakhle, H., Smith, L., Bell, S. M., Burns, P. A., Cummings, M., Hanby, A. M., Lane, S., Parker, M. D., Hughes, T. A., Speirs, V."Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region". International Journal of Oncology 43.6 (2013): 2039-2045.
Chicago
Al-Nakhle, H., Smith, L., Bell, S. M., Burns, P. A., Cummings, M., Hanby, A. M., Lane, S., Parker, M. D., Hughes, T. A., Speirs, V."Regulation of estrogen receptor β1 expression in breast cancer by epigenetic modification of the 5' regulatory region". International Journal of Oncology 43, no. 6 (2013): 2039-2045. https://doi.org/10.3892/ijo.2013.2112
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