Gene expression changes upon the ablation of mesenchymal androgen receptor (AR) in the mouse mesonephroi
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1031640 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26500100_1.fastq.gz | Fastqsanger.gz | |||
| SRR26500100_2.fastq.gz | Fastqsanger.gz | |||
| SRR26500101_1.fastq.gz | Fastqsanger.gz | |||
| SRR26500101_2.fastq.gz | Fastqsanger.gz | |||
| SRR26500102_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Wolffian duct maintenance and differentiation is predominantly driven by the androgen action, which is mediated by the androgen receptor (AR). It is well established that the mesenchyme indicates the fate and differentiation of epithelial cells. However, in vivo developmental requirement of mesenchymal AR in Wolffian duct development is still undefined. By designing a mesenchyme-specific Ar knockout (ARKO), we discovered that the loss of mesenchymal Ar led to the bilateral or unilateral degeneration of caudal Wolffian ducts and cystic formation at the cranial Wolffian ducts. Ex vivo culture of ARKO Wolffian ducts invariably resulted in bilateral defects, suggesting that some factor(s) originating from surrounding tissues in vivo might promote Wolffian duct survival and growth even in the absence of mesenchymal Ar. Mechanistically, we found cell proliferation was significantly reduced in both epithelial and mesenchymal compartments; but cell apoptosis was not affected. Transcriptomic analysis by RNA-seq revealed differentially expressed genes associated with morphological and cellular changes in ARKO male embryos (i.e. reduced cell proliferation and decreased number of epithelial cells). Mesenchymal differentiation into smooth muscle cells that are critical for morphogenesis was also impaired in ARKO male embryos. Taken together, our results demonstrate the crucial roles of the mesenchymal AR in Wolffian duct maintenance and morphogenesis in mice.
2024-01-10 | GSE246141 | GEO
Project description:We report that TRAF4-mediated AR ubiquitination alters AR genomic binding profile under androgen deprivation condition.
2023-05-24 | GSE154001 | GEO
Project description:To identify the genes regulated by the androgen receptor (AR), we performed RNA-seq in the U2OS-AR cell line (derived from U2OS ATTC:HTB-96, stably transfected with an expression construct for human AR), upon androgen (R1881) or vehicle (DMSO) treatment for 24 hours.
2021-03-09 | E-MTAB-9622 | biostudies-arrayexpress
Project description:Genome-wide AR binding under androgen deprivation condition upon TRAF4 overexpression
| PRJNA644792 | ENA
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated genes, CTBP2, FOXP1 and RUNX1. These factors interact with AR ligand dependently. In order to investigate androgen-regulated gene functions in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siRNA treatment. We also treated cells with vehicle or androgen to analyzed the effects of these genes on AR function. Observation of androgen dependent gene expression changes after treatment with siRNAs targeting FOXP1, CTBP2 and FOXA1 with microarray.
2014-10-21 | E-GEOD-58309 | biostudies-arrayexpress
Project description:Androgens exert their effects primarily by binding to the androgen receptor (AR), a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skele- tal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via nonmyofiber cells. In this context, the cellular and molecular mechanisms of AR in mesenchymal progenitors, which play a crucial role in maintaining skeletal muscle homeostasis, remain largely unknown. In this study, we demonstrated expression of AR in mesenchymal progenitors and found that targeted AR ablation in mesenchymal progenitors reduced limb muscle mass in mature adult, but not young or aged, male mice, although fatty infiltration of muscle was not affected. The absence of AR in mesenchymal progenitors led to remarkable perineal muscle hypotrophy, regard- less of age, due to abnormal regulation of transcripts associated with cell death and extracellular matrix organization. Additionally, we revealed that AR in mesenchymal progenitors regulates the expression of insulin-like growth factor 1 (Igf1) and that IGF1 administration prevents perineal muscle atrophy in a paracrine manner. These findings indicate that the anabolic effects of androgens regulate skeletal muscle mass via, at least in part, AR signaling in mesenchymal progenitors.
2023-11-22 | GSE247378 | GEO
Project description:Androgen Receptor (AR) variants (AR-V) drive prostate cancer (PCa) resistance to first and second-generation therapies targeting endocrine regulation of AR. To understand the sets of genomic targets of full-length AR vs. AR-Vs, we conducted genome-wide ChIP-seq using isogenic pairs of genome engineering cell lines expressing either ARv567es (R1-D567) or full-length AR (R1-AD1). Our data demonstrate that androgen-activated full-length AR and AR-Vs both bind to similar genomic targets, which are enriched for high affinity androgen response elements (AREs). Overall, this study demonstrates that AR-Vs restore the broad AR cistrome that is otherwise lost during endocrine-targeted therapy.
2015-03-13 | GSE61838 | GEO
Project description:The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a “first-in-field” approach to target AR expression and function and improve outcomes in CRPC. LNCaP cells were transfected with control siRNA (3), GATA2 siRNA (3) or AR siRNA for 72 hours.
2015-01-21 | E-GEOD-63539 | biostudies-arrayexpress
Project description:Prostate embryonic development, pubertal and adult growth, maintenance, and regeneration are regulated through androgen signaling-mediated mesenchymal epithelial interactions. Specifically, the essential role of mesenchymal androgen signaling in the development of prostate epithelium has been observed for over 30 years. However, the identity of the mesenchymal cells responsible for this paracrine regulation and related mechanisms are still unknown. Here, we provide the first demonstration of an indispensable role of the androgen receptor (AR) in sonic hedgehog (SHH) responsive Gli1-expressing cells, in regulating prostate development, growth, and regeneration. Selective deletion of AR expression in Gli1-expressing cells during embryogenesis disrupts prostatic budding and impairs prostate development and formation. Tissue recombination assays showed that urogenital mesenchyme (UGM) containing AR-deficient mesenchymal Gli1-expressing cells combined with wildtype urogenital epithelium (UGE) failed to develop normal prostate tissue in the presence of androgens, revealing the decisive role of AR in mesenchymal SHH responsive cells in prostate development. Prepubescent deletion of AR expression in Gli1 expressing cells resulted in severe impairment of androgen-induced prostate growth and regeneration. RNA-sequencing analysis showed significant alterations in signaling pathways related to prostate development, stem cells, organ morphogenesis appeared showed significant changes in AR-deficient Gli1-expressing cells. The transforming growth factor β (TGFβ) pathway was up-regulated in AR-deficient Gli1-expressing cells. We further demonstrated the activation of TGF- b signaling in AR deleted prostatic Gli1-expressing cells, which inhibits prostate epithelium growth through paracrine regulation. These data demonstrate a novel role of the AR in the Gli1-expressing cellular niche for regulating prostatic cell fate, morphogenesis, and renewal, and elucidate the mechanism by which mesenchymal androgen-signaling through SHH-responsive cells elicits the growth and regeneration of prostate epithelium.
2020-01-03 | GSE140823 | GEO
Project description:Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.
2007-05-04 | E-SMDB-4028 | biostudies-arrayexpress