The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Olli Jänne
PROVIDER: E-GEOD-31341 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We report that the phytoestrogen genistein acts as a tissue-specific androgen receptor modulator in mouse using a novel androgen reporter mouse line and gene expression profiling. Genistein is a partial androgen agonist/antagonist in prostate, brain, and testis but not in skeletal muscle or lung. Gene expression profiling has been done from prostates of intact and castrated male mice treated with genistein or vehicle. Gene expression profiling was also done from prostates of estradiol-treated intact male mice.
2011-08-19 | GSE31341 | GEO
Project description:Androgen is critical for the growth of the murine prostate. Castration removes the predominant source of androgen in the mouse, leading to prostatic atrophy and death of epithelial cells. However, studies show that epithelial cells which remain in the castrated prostate are enriched for progenitor activity compared to the intact prostate. We performed gene expression profiling of basal and luminal epithelial cells isolated from paired intact and castrated adult male C57BL/6 mouse prostates to gain insights into the mechanisms promoting survival in castration-resistant epithelial cells.
2015-12-03 | GSE75628 | GEO
Project description:To understand the dynamic changes of different cell populations within the Pten-null prostate cancer model in response to ADT, we carried out scRNA-seq transcriptome analysis on CD45- and CD45+ FACS-sorted cells from Pten-null intact (CP), early-(CRPC-4wks) and late-(CRPC-12wks) stage castrated prostates, respectively. To systematically investigate the effects of androgen deprivation therapy (ADT) on the cellular landscapes of primary and CRPC as well as intra- and extra-tumoral immune cells and their functional status at single cell level, we conducted scRNA-seq on CD45+ cells from bone marrow, blood, spleen and thymus of intact, early- and late-stage castrated Pten-null mice.
2025-06-18 | GSE270744 | GEO
Project description:To understand the dynamic changes of different cell populations within the Pten-null prostate cancer model in response to ADT, we carried out scRNA-seq transcriptome analysis on CD45- and CD45+ FACS-sorted cells from Pten-null intact (CP), early-(nmCRPC-4wks) and late-(nmCRPC-12wks) stage castrated prostates, respectively. To systematically investigate the effects of androgen deprivation therapy (ADT) on the cellular landscapes of primary and nmCRPC as well as intra- and extra-tumoral immune cells and their functional status at single cell level, we conducted scRNA-seq on CD45+ cells from bone marrow, blood, spleen and thymus of intact, early- and late-stage castrated Pten-null mice.
2024-11-29 | GSE270743 | GEO
Project description:G-1 is an agonist to GPR30. Activation of GPR30 by G-1 inhibited prostate cancer cell growth in LNCaP xenografts regrown after catration of the host (nude mice), but not in the androgen-sensitive LNCaP xenograft grown in an intact host. Results provide insights into the molecular basis of G-1 action in castration-resistant prostate cancer. Male nude mice were injected with LNCaP cells. When the LNCaP tumors reached 150–300 mm3, mice were divided into two groups: intact (androgen-sensitive tumor) and castrated. For the intact group, mice were subcutaneously injected with vehicle alone (95% PBS, 2.5% DMSO, 2.5% ethanol) or G-1 (4 mg/kg/day in vehicle) daily for 16 days. For the castrated group, tumors regressed and then regrew to ~300-400mm3. Mice were treated daily with vehicle or G-1 as described for 16 days. Tumors were harvested for RNA extraction and microarray experiments.
2014-02-14 | E-GEOD-54974 | biostudies-arrayexpress
Project description:Androgens are required for prostate development, growth and physiology, by activating the androgen receptor (AR) upon activation by testosterone and dihydrotestosterone (DHT), the AR undergoes conformational changes, dimerizes and translocates to the cell nucleus regulation important genes releted to cell survival. Understanding the mechanisms of androgen regulation in the prostate gland is important, because the prostate is affected by several different diseases, in particular prostate cancer (PCa). Several ways exist to treat prostate cancer and promote epithelial cell death. Treatments involving androgen manipulation include surgical castration (bilateral orchiectomy), antiandrogens (usually AR antagonists), or substances that inhibit androgen synthesis (5 alpha-reductase inhibitors, gonadotrophin-releasing hormone blockers). 17 beta-estradiol exerts anti-androgen effects by blocking the hypothalamic production of gonadotropin-releasing hormone and thereby inhibiting the production of testosterone by the testes , but also acts locally via interactions with either of the estrogen receptors found in the gland. It is known that the kinetics of apoptosis are different in the rat ventral prostate (VP) of castrated rats (Cas group) and in rats subjected to 17 beta-estradiol high dose (group E2) or their combination (group Cas+E2), with an evident additive effect in the latter situation (Garcia-Florez et al, 2005). The microarray approach was done to figure out what genes are expressed and how the cells of ventral prostate gland responses when the androgen is not available comparing three diferent androgen deprivation methods (sirurgical castration, high dose of 17-beta estradiol and both treatment combined). Forty-eight 21-day-old male Wistar rats were obtained from the Multidisciplinary Center for Biological Research (CEMIB), University of Campinas. The animals were kept under normal light conditions (12-h light:dark cycle) and received filtered tap water and Purina rodent chow ad libitum. On the 90th day after birth, the rats were divided in four groups (n=3) and assigned to different treatment groups. To cause androgen deprivation, we utilized three different procedures with different effects on epithelial cell apoptosis. Animals in the first group were castrated (Cas) by orchiectomy via scrotal incision under ketamine (150 mg/Kg body weight) and xylazin (10 mg/kg body weight) anesthesia. Animals in the second group received a 25 mg/Kg body weight dose of 17β-estradiol diluted in corn oil (E2 group). The third group received a combination of both treatments (Cas+E2 group) (combined orchiectomy and 17β-estradiol). In the control group (Ct; normal androgen and estrogen), the animals received only the vehicle. Three days after the treatments, the rats were killed by anesthetic overdose, and the ventral prostate was dissected out for the microarray and immunohistochemistry analyses.
2015-03-28 | E-GEOD-56289 | biostudies-arrayexpress
Project description:Analysis of transcriptome of prostate tissue from the anterior lobe or tumor from 9, 12, 13, 14, and 16 months old mouse Prostate tissue or tumor from 9 month old Nkx3.1CreERT2/+ mice, 14 month old Nkx3.1CreERT2/+;Ptenflox/flox mice (intact, treated with vehicle), 16 month old Nkx3.1CreERT2/+;Ptenflox/flox mice (castrated, treated with vehicle or abiraterone), 12 month old Nkx3.1CreERT2/+;Ptenflox/flox;P53flox/flox mice(intact, treated with vehicle), 13 month old Nkx3.1CreERT2/+;Ptenflox/flox;P53flox/flox mice (castrated, treated with vehicle or abiraterone) was harvested, and snap frozen for subsequent molecular analysis
2017-04-18 | GSE92721 | GEO
Project description:In this study, we used microarray analysis to determine gene expression profile changes in the mouse prostate following castration and hormone replacement. We first identified genes with significant expression changes in each of these two processes and then generated a list of androgen responsive genes and a list of genes whose expression were inversely correlated with the presence of androgen. The analysis of this data set is described in Wang et al., Differentiation, 2006 Experiment Overall Design: C57/B6 mice of 10-12 weeks old (Charles River, Hollister, CA) were used. Mice were castrated, and at 3 or 14 days after surgery (C3 or C14), mice from these groups were sacrificed and whole prostates were collected. Prostates were also collected from sham-treated mice for control (N3). To obtain re-growing or regenerating prostate, mice that had been castrated 14 days before were implanted with testosterone (T) pellet (15 mg/pellet/mouse, Innovative Research, Sarasota, FL). Three days after pellet implantation, mice were sacrificed and prostates were collected (C14+T3). Five mice were used for each treatment/time point. Total RNA was purified with RNeasy kit.
2009-04-10 | E-GEOD-5901 | biostudies-arrayexpress
Project description:Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen-deprivation remain poorly described despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild type mouse prostates a rare population of luminal progenitor cells that we called LSCmed according to their FACS profile (Lin?/Sca-1+/CD49fmed). Here we investigated the prevalence and castration resistance of LSCmed in various mouse models of prostate tumorigenesis. In intact mice, we show that LSCmed prevalence remains low (5-10% of epithelial cells) when prostatic androgen receptor signaling unaltered (malignant Hi-Myc mice) but significantly increases in models exhibiting reduced prostatic androgen receptor signaling, rising up to 30% in premalignant tumors (Pb-PRL mice) and to >80% in castration-resistant prostate tumors driven by Pten loss (Ptenpc-/- mice). LSCmed tolerance to androgen deprivation was demonstrated by their persistence (Ptenpc-/-) or further enrichment (Pb-PRL) 2-3 weeks after castration as evidenced by FACS analysis. Transcriptomic analysis revealed that LSCmed represent a unique cell entity as their gene-expression profile is different from luminal and basal/stem cells, but shares markers of each. Their intrinsic androgen signaling is markedly decreased, which explains why LSCmed tolerate androgen-deprivation. This also enlightens why Ptenpc-/- tumors are castration-resistant since LSCmed represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSCmed on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSCmed in various mouse prostate specimens. In castrated Ptenpc-/- prostates, BrdU staining revealed massive proliferation of CK4+ cells, further demonstrating their key role in castration-resistant prostate cancer progression. In all, this study identifies LSCmed as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate-resistant prostate cancer.
2017-08-15 | E-MTAB-4991 | biostudies-arrayexpress
Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.
2018-08-22 | GSE116299 | GEO