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A tumor suppressive relationship between mineralocorticoid and retinoic receptors activates a transcriptional program consistent with a reverse Warburg effect in breast cancer

ABSTRACT: A tumor suppressive relationship between mineralocorticoid and retinoic receptors activates a transcriptional program consistent with a reverse Warburg effect in breast cancer

PROVIDER: PRJNA673399 | ENA |

REPOSITORIES: ENA

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A tumor suppressive relationship between mineralocorticoid and retinoic receptors activates a transcriptional program consistent with a reverse Warburg effect in breast cancer

Project description:Whole transcriptome profiling in MR inducible MCF-7 cells after combinations of ligand treatments

2020-10-31 | GSE160497 | GEO

A tumour suppressive relationship between mineralocorticoid and retinoic acid receptors activates a transcriptional program consistent with a reverse Warburg effect in breast cancer.

Project description:BackgroundThe role of nuclear receptors in both the aetiology and treatment of breast cancer is exemplified by the use of the oestrogen receptor (ER) as a prognostic marker and treatment target. Treatments targeting the oestrogen signalling pathway are initially highly effective for most patients. However, for the breast cancers that fail to respond, or become resistant, to current endocrine treatments, the long-term outlook is poor. ER is a member of the nuclear receptor superfamily, comprising 48 members in the human, many of which are expressed in the breast and could be used as alternative targets in cases where current treatments are ineffective.MethodsWe used sparse canonical correlation analysis to interrogate potential novel nuclear receptor expression relationships in normal breast and breast cancer. These were further explored using whole transcriptome profiling in breast cancer cells after combinations of ligand treatments.ResultsUsing this approach, we discovered a tumour suppressive relationship between the mineralocorticoid receptor (MR) and retinoic acid receptors (RAR), in particular RARβ. Expression profiling of MR expressing breast cancer cells revealed that mineralocorticoid and retinoid co-treatment activated an expression program consistent with a reverse Warburg effect and growth inhibition, which was not observed with either ligand alone. Moreover, high expression of both MR and RARB was associated with improved breast cancer-specific survival.ConclusionOur study reveals a previously unknown relationship between MR and RAR in the breast, which is dependent on menopausal state and altered in malignancy. This finding identifies potential new targets for the treatment of breast cancers that are refractory to existing therapeutic options.

| S-EPMC7641839 | biostudies-literature

Molecular signature of mineralocorticoid signalling in cardiomyocytes

2010-06-18 | GSE20525 | GEO

Effect of Mineralocorticoid Receptor deletion on glucocorticoid signalling in the macropahge

2010-07-30 | GSE23308 | GEO

Molecular signature of mineralocorticoid signalling in cardiomyocytes

Project description:Gene expression analysis of hearts from double transgenic mice with conditional, cardiomyocyte-specific, overexpression of the mineralocorticoid (MR) or of the glucocorticoid receptor (GR). GR-mice vs controls, MR-mice vs controls. GR: 3 sample pools hybridized to 2 microarrays each. MR: 1 sample pool hybridized to 3 microarrays. Microarray contains triplicate spots.

2010-06-18 | E-GEOD-20525 | biostudies-arrayexpress

Smooth muscle cell mineralocorticoid receptor regulation of vascular mRNAs with aging

Project description:We used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic mRNA to examine the effect of age on vascular mRNA alterations in the presence and absence of SMC-MR. For more information about the mouse model see: McCurley, A et al. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med. 2012 Sep;18(9):1429-33

2017-08-10 | GSE102397 | GEO

Smooth muscle cell mineralocorticoid receptor regulation of vascular microRNAs with aging

Project description:We used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic miRNA to examine the effect of age on vascular miRNA alterations in the presence and absence of SMC-MR. For more information about the mouse model see: McCurley, A et al. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med. 2012 Sep;18(9):1429-33

2016-07-29 | GSE84960 | GEO

Cistrome of the Aldosterone-activated Mineralocorticoid Receptor in Human Renal Cells

Project description:Aldosterone, the main mineralocorticoid hormone in Humans, has a major role in maintaining the hemo-electrolytique homeostasis, by acting in the distal part of nephron. This steroid hormone mainly acts through its binding to a ligand-induced transcription factor, the mineralocorticoid receptor (MR). MR binds to specific genomic sequences, where it recruits transcriptional coregulators, to activate or repress target gene transcription. The aim of this work was to access the whole aldosterone-dependand MR target genes, by comparing sequenced data from aldosterone or vehicle-treated samples. Anti-MR ChIP-seq in Human Kidney GFP-hMR cells treated with vehicle or Aldosterone.

2015-06-12 | E-GEOD-69777 | biostudies-arrayexpress

Smooth muscle cell mineralocorticoid receptor regulation of vascular microRNAs with aging

2016-07-29 | E-GEOD-84960 | biostudies-arrayexpress

Effect of Mineralocorticoid Receptor deletion on glucocorticoid signalling in the macropahge

Project description:Inappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, is associated with increased inflammation and risk of cardiovascular disease. MR antagonists are cardioprotective and antiinflammatory in vivo, and evidence suggests that they mediate these effects in part by aldosterone- independent mechanisms. We used affymetrix to characterize the effect of Mineralocorticoid Receptor deletion on macrophage transcriptional profile, and identify its requirement in normal glucocorticoid signalling. We isolated mouse peritoneal macrophages from Myeloid MRKO mice and Floxed Controls, cultured in the presence or absence of corticosterone. RNA was extracted for Affymetrix cDNA hybridization. Each sample was pooled from experiments performed in triplicate.

2010-07-30 | E-GEOD-23308 | biostudies-arrayexpress

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