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Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance

Albrecht, Juliane LU orcid ; Müller, Mirjam LU ; Hafstað, Völundur LU ; Kaminska, Kamila LU ; Vallon-Christersson, Johan LU orcid ; Honeth, Gabriella LU and Persson, Helena LU orcid (2025) In Molecular Oncology 19(1). p.204-224
Abstract

Oestrogen receptor alpha (ER; gene symbol ESR1) is the most important prognostic and treatment-predictive biomarker in breast cancer. Drugs targeting oestrogen and ER for endocrine therapy of breast cancer include aromatase inhibitors, the selective ER modulator tamoxifen and the selective ER degrader fulvestrant. Tumours can develop resistance to endocrine therapy through several mechanisms, which is often linked to altered expression of ER. To investigate the role of promoter methylation in the regulation of ESR1 expression, we used bisulfite sequencing to measure methylation at CpG sites in alternative ER promoter regions for six cell line models of fulvestrant resistance. Both CpG methylation and expression of alternative first... (More)

Oestrogen receptor alpha (ER; gene symbol ESR1) is the most important prognostic and treatment-predictive biomarker in breast cancer. Drugs targeting oestrogen and ER for endocrine therapy of breast cancer include aromatase inhibitors, the selective ER modulator tamoxifen and the selective ER degrader fulvestrant. Tumours can develop resistance to endocrine therapy through several mechanisms, which is often linked to altered expression of ER. To investigate the role of promoter methylation in the regulation of ESR1 expression, we used bisulfite sequencing to measure methylation at CpG sites in alternative ER promoter regions for six cell line models of fulvestrant resistance. Both CpG methylation and expression of alternative first exons changed dynamically, with striking differences between cell lines that had stable or unstable resistance upon fulvestrant withdrawal. Methylation at some CpG sites was strongly negatively correlated with expression of specific first exons. In a breast tumour cohort, higher relative expression of upstream alternative first exons was associated with worse prognosis in post-menopausal women with ER-positive tumours who received endocrine therapy.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Oncology
volume
19
issue
1
pages
204 - 224
publisher
Elsevier
external identifiers
  • scopus:85200469148
  • pmid:39108022
ISSN
1574-7891
DOI
10.1002/1878-0261.13713
language
English
LU publication?
yes
additional info
© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
id
75bbda9a-6a7c-4ec6-ac41-748310189174
date added to LUP
2024-08-08 09:03:08
date last changed
2025-01-31 18:52:19
@article{75bbda9a-6a7c-4ec6-ac41-748310189174,
  abstract     = {{<p>Oestrogen receptor alpha (ER; gene symbol ESR1) is the most important prognostic and treatment-predictive biomarker in breast cancer. Drugs targeting oestrogen and ER for endocrine therapy of breast cancer include aromatase inhibitors, the selective ER modulator tamoxifen and the selective ER degrader fulvestrant. Tumours can develop resistance to endocrine therapy through several mechanisms, which is often linked to altered expression of ER. To investigate the role of promoter methylation in the regulation of ESR1 expression, we used bisulfite sequencing to measure methylation at CpG sites in alternative ER promoter regions for six cell line models of fulvestrant resistance. Both CpG methylation and expression of alternative first exons changed dynamically, with striking differences between cell lines that had stable or unstable resistance upon fulvestrant withdrawal. Methylation at some CpG sites was strongly negatively correlated with expression of specific first exons. In a breast tumour cohort, higher relative expression of upstream alternative first exons was associated with worse prognosis in post-menopausal women with ER-positive tumours who received endocrine therapy.</p>}},
  author       = {{Albrecht, Juliane and Müller, Mirjam and Hafstað, Völundur and Kaminska, Kamila and Vallon-Christersson, Johan and Honeth, Gabriella and Persson, Helena}},
  issn         = {{1574-7891}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{204--224}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Oncology}},
  title        = {{Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance}},
  url          = {{http://dx.doi.org/10.1002/1878-0261.13713}},
  doi          = {{10.1002/1878-0261.13713}},
  volume       = {{19}},
  year         = {{2025}},
}