Dataset Information

ER/PR RIME Experiments in MCF7 and T47D cell lines

ABSTRACT: Immuno-precipitation followed by MS was performed using the RIME protocol in this study. Estrogen Receptor (ER) and Progestorone Receptor (PR) were targetted using antibodies. The experiments were performed in a quantitative manner using SILAC labelling. Cells grown in complete serum (estrogenic) conditions were compared against an cells in similar complete media, however supplemented with Progesterone (PG) or R5020 for 4 hours. Experiments were performed in MCF7 and T47D cell lines

OTHER RELATED OMICS DATASETS IN: PRJNA282506PRJNA282502PRJNA282507PRJNA282508PRJNA282505

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Hisham Mohammed

LAB HEAD: Dr Jason Carroll

PROVIDER: PXD002104 | Pride | 2015-05-26

REPOSITORIES: Pride

ACCESS DATA

Publications

Progesterone receptor modulates ERα action in breast cancer.

Mohammed Hisham H Russell I Alasdair IA Stark Rory R Rueda Oscar M OM Hickey Theresa E TE Tarulli Gerard A GA Serandour Aurelien A AA Birrell Stephen N SN Bruna Alejandra A Saadi Amel A Menon Suraj S Hadfield James J Pugh Michelle M Raj Ganesh V GV Brown Gordon D GD D'Santos Clive C Robinson Jessica L L JL Silva Grace G Launchbury Rosalind R Perou Charles M CM Stingl John J Caldas Carlos C Tilley Wayne D WD Carroll Jason S JS

Nature 20150708 7560

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibi ...[more]

PMID: 26153859

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Project description:The glucocorticoid receptor (GR) regulates gene expression throughout the human genome in a cell-type-specific manner, governing various aspects of homeostasis. The influence of this transcriptional regulator is seen in multiple pathologies, including cancer. Pharmacological activation of the GR is frequently used to alleviate side-effects caused by therapy for patients with various non-lymphoid solid (i.e. non-hematologic) cancers; however, prior studies have shown that this treatment might also have anti-proliferative action on cancer cells. Nonetheless, the molecular underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the molecular mechanisms of glucocorticoid response in non-lymphoid solid cancers models, focusing on lung cancer. Activation of the GR induces reversible cancer cell dormancy in which cells are tolerant to large array of anti-cancer drugs. This state transition is accompanied by induction of growth factor survival signalling (IGF-1R) and acquired vulnerability to inhibitors of this pathway, both in vitro and in vivo. The observed phenotype is dependent on a single GR target gene - CDKN1C, which encodes for a cell cycle inhibitor protein p57. We have discovered an upstream distal enhancer of CDKN1C, which through GR-induced chromatin looping regulates the expression of this key gene, as confirmed in human tumour specimens. Furthermore, we demonstrate that the SWI/SNF complex composition fine-tunes the GR transcriptional activity at the CDKN1C locus, allowing for precise regulation of cell dormancy induction. Collectively, we show that SWI/SNF-facilitated regulation of CDKN1C underlines GR-induced reversible drug-tolerant state in cancer cells. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anti-cancer therapy related side-effects.

Dataset Information

ER/PR RIME Experiments in MCF7 and T47D cell lines

Publications

Progesterone receptor modulates ERα action in breast cancer.

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