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| Status |
Public on Oct 04, 2018 |
| Title |
Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by Regulating DNA Methylation in Breast Cancer Cells |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
How breast cancers respond to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively), with doublenegative ER-/PR- breast cancers having worse clinical outcome than ER+/PR+ breast cancers. Although much is known about ERα gene (ESR1) regulation after hormonal stimulation, how it is regulated in the absence of hormones is not fully understood. We used ER+/PR+ positive breast cancer cells to investigate the role of PR in ESR1 gene regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and the DNA methylation profile 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 DNA 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. Consequently, the rescue of PR expression in PR-depleted cells is insufficient to restore ESR1 expression. Consistent with these data, DNA methylation impedes PR binding to consensus progesterone responsive elements in vitro. These findings help us understand the complex crosstalk between PR and ER, and suggest that the analysis of DNA methylation of ESR1 promoter in breast cancer cells can help to design the appropriate targeted therapies for different types of breast cancer patients.
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| Overall design |
DNA methylation analysis in hormone-deprived T47D breast cancer cells
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| Contributor(s) |
Verde G, De Llobet LI, Wright RH, Quilez J, Peiró S, Le Dily F, Beato M |
| Citation(s) |
30301163 |
| Submission date |
Dec 12, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
François Le Dily |
| E-mail(s) |
francois.ledily@crg.eu
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| Organization name |
CRG-Centre for Genomic Regulation
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| Street address |
Dr. Aiguader, 88
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| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (1) |
| GSM2884396 |
DNA methylation in hormone-free T47D breast cancer cells |
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| Relations |
| BioProject |
PRJNA422054 |
| SRA |
SRP126550 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107966_RAW.tar |
974.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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