GSE107966 Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by Regulating DNA Methylation in Breast Cancer Cells

Contributors : Gaetano Verde ; Lara I De Llobet ; Roni H Wright ; Javier Quilez ; Sandra Peir ó ; François Le Dily ; Miguel BeatoSeries Type : Methylation profiling by high throughput sequencingOrganism : Homo sapiensHow 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 ER α 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 ESR 1 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-de pleted 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 progestero ne responsive elements in vitro. These findings help us understand the complex crossta...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Homo sapiens Source Type: research