Unliganded progesterone receptor governs estrogen receptor gene expression by regulating DNA methylation in breast cancer cells
Author
Verde, Gaetano
Lara, de Llobet
Wright, Roni
Quilez, Javier
Peiró, Sandra
Le Dily, François
Beato, Miguel
Publication date
2018ISSN
2072-6694
Abstract
Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ERα gene (ESR1) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells. Depletion of PR reduces ESR1 expression, with a concomitant increase in gene promoter methylation. The high amount of methylation in the ESR1 promoter of PR-depleted cells persists after the stable re-expression of PR and inhibits PR binding to this genomic region. As a consequence, the rescue of PR expression in PR-depleted cells is insufficient to restore ESR1 expression. Consistently, DNA methylation impedes PR binding to consensus progesterone responsive elements. These findings contribute to understanding the complex crosstalk between PR and ER and suggest that the analysis of ESR1 promoter methylation in breast cancer cells can help to design more appropriate targeted therapies for breast cancer patients.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
57 - Biological sciences in general
61 - Medical sciences
Keywords
Receptor de progesterona
Receptor d'estrògens
Expressió gènica
Metilació de l'ADN
Càncer de pulmó
Teràpia endocrina
ADN
Receptor de progesterona
Receptor de estrógeno
Expresion genica
Metilación del ADN
Cáncer de mama
Terapia endocrina
ADN
Progesterone receptor
Estrogen receptor
Gene expression
DNA methylation
Breast cancer
Endocrine therapy
DNA
Pages
15
Publisher
MDPI
Collection
10;10
Is part of
Cancers
Citation
Verde, Gaetano; De Llobet, Lara I.; Wright, Roni H.G. [et al.]. Unliganded progesterone receptor governs estrogen receptor gene expression by regulating DNA methylation in breast cancer cells. Cancers, 2018, 10(10), 371. Disponible en: <https://www.mdpi.com/2072-6694/10/10/371>. Fecha de acceso: 26 ene. 2022. DOI: 10.3390/cancers10100371.
This item appears in the following Collection(s)
- Ciències Bàsiques [65]
Rights
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/deed.ca