The reprogrammation of the estrogen and androgen responses in murine prostate cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE254635 | GEO | 2024/04/19
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of the study was to identify the genes regulated by the estrogen receptor alpha (ERa) in a human prostate cancer cell line (VCaP), with and without the co-activation of the oncogene AR (androgen receptor).
2024-04-19 | GSE256370 | GEO
Project description:The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor a (ERa). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERa negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells.
2016-07-18 | GSE70161 | GEO
Project description:Prostate glands predominantly exhibit androgen dependence, but increasing evidence suggests that estrogen receptor signaling is involved in its development and pathogenesis. By integrating ChIP sequencing for estrogen receptor alpha (ERα) with transcriptome sequencing data from prostate cancer samples, we found ERα to significantly influence the noncoding transcriptome in prostate cancer. We identified one such long noncoding RNA, NEAT1, to play an important role in prostate cancer progression through direct regulation of transcription of its target genes. NEAT1, in an ERα dependent manner, promotes prostate tumorigenesis by interacting with and modulating chromatin state at promoters of prostate cancer specific signature genes. NEAT1 expression is positively correlated with PSMA in prostate adenocarcinoma and with B3GAT1 in neuroendocrine prostate cancer. This study identifies NEAT1 as a novel biomarker or therapeutic target in prostate cancer and also suggests that co-targeting ERα and androgen receptor (AR) may be effective for a subset of patients with advanced prostate cancer and with NEAT1 overexpression. mRNA profiles of MEF cell lines prepared from E13.5 embryos of wild-type (WT) and NEAT1 knockout (KO; NEAT1−/−) mice were generated by deep sequencing, using Illumina HiSeq 2000. Strand specific mRNA profiles of VCaP and VCaP ERa cell lines were generated by deep sequencing, using Illumina GA IIx.
2014-12-01 | GSE43986 | GEO
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice
2007-06-01 | GSE7798 | GEO
Project description:Estrogen receptor beta excerts tumorsuppressive effects in prostate cancer through repression of androgen receptor activity
| PRJNA604972 | ENA
Project description:Aberrant androgen receptor (AR)-mediated transcription is a critical driver in progression of human prostate cancer. It's known that different doses of androgens can elicit differential transcriptional and proliferative responses in prostate-tumor cells. Here, we set out to examine the androgenic regulation of glycoprotein expression in the membrane fraction of prostate-tumor cells that could serve as mediators or markers of androgen-induced proliferative responses observed in prostate-tumor cells. A bioanalytical workflow involving lectin-affinity chromatography and label-free quantitative mass spectrometry was used to identify androgen-sensitive glycomembrane protein expression associated with androgen-mediated proliferation. This study would facilitate the identification of surface membrane proteins involved in androgen-mediated proliferation and provide potential therapeutic targets in the detection treatment of proliferation prostate-tumors.
2022-03-01 | PXD002913 | Pride
Project description:Androgens are central to prostate cancer (PCa) development and targeting this pathway is currently the main therapeutic axis in the clinic, but the mechanism by which androgen signaling contributes to the oncometabolic state of PCa cells remains to be fully elucidated. The intersection of gene expression, binding-events and motif finding analyses following androgen exposure identified a metabolic gene signature associated with the action of estrogen-related receptors (ERRs). Unexpectedly, we show that ERRγ acts as a negative regulator of mitochondrial respiration in the context of PCa, and that AR-dependent direct repression of ERRγ promotes the reactivation of a functional TCA cycle. This metabolic state, which parallels the loss of ERRγ expression, was observed in both androgen-dependent and castration-resistant PCa and was associated with cell proliferation. Interrogation of several clinical studies revealed a strong inverse relationship between ERRγ expression and the severity of the disease. Our study uncovers a novel mechanism by which AR-dependent repression of ERRγ contributes to the reprogramming of PCa cell metabolism to favor mitochondrial activity and cell proliferation. We used microarrays to investigate the transcriptional regulation of metabolic genes by 72h treatment with R1881, a synthetic androgens, with or without repression of the estrogen-related receptor gamma, in LNCaP prostate cancer cells.
2016-12-06 | GSE86781 | GEO
Project description:Prostate glands predominantly exhibit androgen dependence, but increasing evidence suggests that estrogen receptor signaling is involved in its development and pathogenesis. By integrating ChIP sequencing for estrogen receptor alpha (ERα) with transcriptome sequencing data from prostate cancer samples, we found ERα to significantly influence the noncoding transcriptome in prostate cancer. We identified one such long noncoding RNA, NEAT1, to play an important role in prostate cancer progression through direct regulation of transcription of its target genes. NEAT1, in an ERα dependent manner, promotes prostate tumorigenesis by interacting with and modulating chromatin state at promoters of prostate cancer specific signature genes. NEAT1 expression is positively correlated with PSMA in prostate adenocarcinoma and with B3GAT1 in neuroendocrine prostate cancer. This study identifies NEAT1 as a novel biomarker or therapeutic target in prostate cancer and also suggests that co-targeting ERα and androgen receptor (AR) may be effective for a subset of patients with advanced prostate cancer and with NEAT1 overexpression.
2014-12-01 | GSE43985 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE30622: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [Expression Array] GSE30623: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [ChIP_seq, DHS_seq] Refer to individual Series
2011-09-13 | E-GEOD-30624 | biostudies-arrayexpress
Project description:Estrogen receptor alpha (ERa) has generally been thought to be transcriptionally inactive until it binds estrogen. Here we show that unliganded ERa, far from being transcriptionally inert, regulates a large number of genes both in vascular endothelial cells (ECs) and in mouse aorta. The genes regulated by unliganded ERa in the aorta (largely composed of smooth muscle cells) differ from those in ECs, and aorta- and EC-regulated promoters show enrichment in binding sites for distinct sets of transcription factors. In vitro, the presence of unliganded ERa decreases the migration and proliferation of ECs, and also increases proliferation of SMCs. Consistent with these effects on individual cells in vitro, mice lacking ERa, in the absence of estrogen, show significantly less SMC proliferation and medial thickening after carotid artery wire injury than ER intact mice. The effects of unliganded ERa on vascular gene expression, cell function in vitro and vascular injury responses in vivo are all reversed by the addition of estrogen. Taken together, these results indicate that unliganded ERa regulates vascular gene expression, vascular cell function, and vascular injury responses, and that the cardiovascular protective effects of estrogen may largely be due to the reversal of these effects of unliganded ERa. These results have important implications for the vascular health of men and post-menopausal women with vascular ERa and low circulating levels of estrogen. This study also raises the possibility that the steroid receptor family could have substantial hormone-independent functions in the vasculature and in other tissues.
2016-11-22 | GSE51535 | GEO