Unknown

Dataset Information

0

PRMT1, a Key Modulator of Unliganded Progesterone Receptor Signaling in Breast Cancer.


ABSTRACT: The progesterone receptor (PR) is a key player in major physiological and pathological responses in women, and the signaling pathways triggered following hormone binding have been extensively studied, particularly with respect to breast cancer development and progression. Interestingly, growing evidence suggests a fundamental role for PR on breast cancer cell homeostasis in hormone-depleted conditions, with hormone-free or unliganded PR (uPR) involved in the silencing of relevant genes prior to hormonal stimulation. We herein identify the protein arginine methyltransferase PRMT1 as a novel actor in uPR signaling. In unstimulated T47D breast cancer cells, PRMT1 interacts and functions alongside uPR and its partners to target endogenous progesterone-responsive promoters. PRMT1 helps to finely tune the silencing of responsive genes, likely by promoting a proper BRCA1-mediated degradation and turnover of unliganded PR. As such, PRMT1 emerges as a key transcriptional coregulator of PR for a subset of relevant progestin-dependent genes before hormonal treatment. Since women experience periods of hormonal fluctuation throughout their lifetime, understanding how steroid receptor pathways in breast cancer cells are regulated when hormones decline may help to determine how to override treatment failure to hormonal therapy and improve patient outcome.

SUBMITTER: Malbeteau L 

PROVIDER: S-EPMC9455263 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

PRMT1, a Key Modulator of Unliganded Progesterone Receptor Signaling in Breast Cancer.

Malbeteau Lucie L   Jacquemetton Julien J   Languilaire Cécile C   Corbo Laura L   Le Romancer Muriel M   Poulard Coralie C  

International journal of molecular sciences 20220823 17


The progesterone receptor (PR) is a key player in major physiological and pathological responses in women, and the signaling pathways triggered following hormone binding have been extensively studied, particularly with respect to breast cancer development and progression. Interestingly, growing evidence suggests a fundamental role for PR on breast cancer cell homeostasis in hormone-depleted conditions, with hormone-free or unliganded PR (uPR) involved in the silencing of relevant genes prior to  ...[more]

Similar Datasets

| S-EPMC6210734 | biostudies-literature
2018-10-04 | GSE107966 | GEO
| S-EPMC6504603 | biostudies-literature
| S-EPMC10088437 | biostudies-literature
| S-EPMC3875321 | biostudies-literature
| S-EPMC3977241 | biostudies-literature
| S-EPMC4045674 | biostudies-literature
| S-EPMC6755991 | biostudies-literature
| S-EPMC5432230 | biostudies-literature
| S-EPMC10208751 | biostudies-literature