ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Progesterone receptor isoform-specific promoter methylation: association of PRA promoter methylation with worse outcome in breast cancer patients.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review.Breast cancer research : BCR · 2020Pooled it
- Structural proteomics defines a sequential priming mechanism for the progesterone receptor.Nature communications · 2025Article
- Molecular Basis of Impaired Decidualization in the Eutopic Endometrium of Endometriosis Patients.Cells · 2025Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- Article
- Unveiling DNA methylation: early diagnosis, risk assessment, and therapy for endometrial cancer.Frontiers in oncology · 2024Review
- Review
- In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers.International journal of molecular sciences · 2023Article
- Expression of Progesterone Receptor A as an Independent Negative Prognosticator for Cervical Cancer.International journal of molecular sciences · 2023Article
- Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer.Breast cancer research : BCR · 2022Article
- Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells.Frontiers in endocrinology · 2022Review
- Upregulation of an estrogen receptor-regulated gene by first generation progestins requires both the progesterone receptor and estrogen receptor alpha.Frontiers in endocrinology · 2022Article
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
- Article
- Progesterone and Breast Cancer: an NCI Workshop Report.Hormones & cancer · 2020Article
- Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma.Journal of ovarian research · 2019Article
- Increased High Molecular Weight FGF2 in Endocrine-Resistant Breast Cancer.Hormones & cancer · 2018Article
- Hypermethylation pattern of ESR and PgR genes and lacking estrogen and progesterone receptors in human breast cancer tumors: ER/PR subtypes.Cancer biomarkers : section A of Disease markers · 2018Article
- CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study.Breast cancer research and treatment · 2017Article
- Progesterone Receptor Isoform Ratio: A Breast Cancer Prognostic and Predictive Factor for Antiprogestin Responsiveness.Journal of the National Cancer Institute · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeERα and PR levels are critical determinants for breast cancer prognosis and response to endocrine therapy. Although PR is known to be silenced by methylation of its promoter, few studies have correlated methylation with PR levels and outcome in breast cancer. There is only one previous small study comparing methylation of the two PR isoforms, PRA and PRB, which are expressed from different promoters, and finally, there is no prior knowledge of associations between isoform-specific methylation and outcome. EXPERIMENTAL
designWe conducted a cohort-based study to test for associations between PRA and PRB methylation, expression, and clinical outcome in tamoxifen-treated patients (n = 500), and in patients who underwent surgery only (n = 500). Methylation and PR levels were measured by bisulfite pyrosequencing and ligand-binding assay, respectively.
resultsLow PR levels were significantly associated with worse outcome in all patients. PRA and PRB promoters were methylated in 9.6% and 14.1% of the breast tumors, respectively. The majority (74%) of PR-negative tumors were not methylated despite the significant inverse correlation of methylation and PR levels. PRA methylation was significantly associated with PRB methylation, although a subset of tumors had PRA only (3.9%) or PRB only (8.3%) methylated. Methylation of PRA, but not PRB was significantly associated with worse outcome in the tamoxifen-treated group.
conclusionsMechanisms other than promoter methylation may be more dominant for loss of PR. Isoform-specific methylation events suggest independent regulation of PRA and PRB. Finally, this article shows for the first time that PRA methylation plays a unique role in tamoxifen-resistant breast cancer.
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