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Calcitriol deregulates AR signaling to inhibit prostate cancer progression in the TRAMP model

ABSTRACT: The mechanism of action of vitamin D in prostate cancer (PCa) remains poorly defined, with most mechanisms identified being highly cell type and model specific. One of the underlying factors for these diverse mechanisms may be the use of overly simplistic in vitro model systems to study the complex biology of vitamin D response. Here we use the more complex and in vivo transgenic adenocarcinoma of mouse prostate (TRAMP) model to better determine the mechanism by which vitamin D inhibits PCa growth. In these studies early stage TRAMP mice were treated M-BM-1 20M-NM-

ORGANISM(S): Mus musculus

SUBMITTER: Dan Wang

PROVIDER: E-GEOD-57382 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Calcitriol deregulates AR signaling to inhibit prostate cancer progression in the TRAMP model

Project description:The mechanism of action of vitamin D in prostate cancer (PCa) remains poorly defined, with most mechanisms identified being highly cell type and model specific. One of the underlying factors for these diverse mechanisms may be the use of overly simplistic in vitro model systems to study the complex biology of vitamin D response. Here we use the more complex and in vivo transgenic adenocarcinoma of mouse prostate (TRAMP) model to better determine the mechanism by which vitamin D inhibits PCa growth. In these studies early stage TRAMP mice were treated ± 20μg/kg calcitriol (vitamin D) on a Monday/Wednesday/Friday schedule and tissue was procured 12 and 24 hours post treatment to assess changes in PCa transcriptomes using Affymetrix gene expression arrays.

2015-03-02 | GSE57382 | GEO

Whole blood leukocytes gene expression in human subjects exposed to printing shop particles

Project description:This study investigates differential expression in human blood leukocytes, from subjects who work in print shops, exposed to particles over time. The time points range over 2 weeks: 1-Monday, 2-Friday, 3-following Monday (rested), and 4-Friday

2020-08-31 | GSE142351 | GEO

Adipose tissue from metabolic syndrome mice induces an aberrant miRNA signature highly relevant in prostate cancer development

Project description:We developed a MeS-like disease model using C57BL/6J mice chronically fed with high fat diet (HFD) that were inoculated with TRAMP-C1 prostate cancer (PCa) cells to investigate the interaction between white adipose tissue (WAT) and PCa cells through miRNAs, in MeS mice. In this dataset, we include the expression data obtained from co-culture medium between TRAMP-C1 cells with HFD-gonadal WAT (gWAT) versus TRAMP-C1 cells with CD-gWAT. For differential expression analysis we used the Rank Product Method.

2020-11-09 | GSE149506 | GEO

Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [ChIP-Seq]

Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates

2015-08-01 | E-GEOD-64656 | biostudies-arrayexpress

Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [Expression profiling]

Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Gene expression profiling in LNCaP cells after 24hr treatment with different nuclear recpetor ligrands, with time-matching control, in triplicates Expression is assayed with Agilent G4112F.

2015-08-01 | E-GEOD-60956 | biostudies-arrayexpress

A phase II study of alternate-day administration of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination as first-line treatment in patients with metastatic colorectal cancer.

Project description:Interventions: S-1 80-120 (mg/day) Monday, Wednesday, Friday, Sunday Leucovorin 50 (mg/day) Monday, Wednesday, Friday, Sunday Oxaliplatin 85 (mg/m2) day1 Bevacizumab 5 (mg/kg) day 1 every 2 weeks Primary outcome(s): Objective response rate as assessed by independent ragiologic review Study Design: Single arm Non-randomized

| 2635716 | ecrin-mdr-crc

Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [ChIP-Seq]

2015-08-01 | GSE64656 | GEO

Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [Expression profiling]

2015-08-01 | GSE60956 | GEO

The small non-coding RNA landscape of prostate epithelium

Project description:Vitamin D, a hormone that acts through the nuclear vitamin D receptor (VDR), upregulates anti-tumorigenic microRNA in prostate epithelium. This may contribute to the lower levels of aggressive prostate cancer (PCa) in patients with high serum vitamin D. Expression of other small non-coding RNAs (ncRNAs) in prostate epithelium and their potential regulation by vitamin D are uncharacterized. Laser capture microdissection (LCM) followed by small-RNA sequencing was used to identify ncRNA in the prostate epithelium of tissues from a vitamin D-supplementation trial. We compared the expression profiles to small-RNA sequencing data from primary prostate epithelial cells and publically-available benign whole prostate. Application of LCM to isolate epithelium promoted sample homogeneity and captured more diversity in ncRNA species. An abundance of PIWI-interacting RNAs (piRNAs) was detected in normal prostate epithelium, which increased under high vitamin D conditions.

2019-04-01 | GSE124589 | GEO

Hsa-miR-1-2/miR-133a-1 cluster expression silencing by DNA hypermethylation triggers oncogenes contributing to prostate cancer aggressiveness

Project description:We developed a metabolic syndrome (MeS)-like disease model using C57BL/6J mice chronically fed with high fat diet (HFD) that were inoculated with TRAMP-C1 prostate cancer (PCa) cells to investigate the effect of a HFD on the expression of cancer-related miRNAs. In this dataset, we include the expression data obtained from TRAMP-C1 tumors developed in control diet (CD) versus high fat diet (HFD) C57BL/6J male mice. For differential expression analysis we used the Rank Product Method for two class unpaired data and a fold discovery rate (FDR) < 0.05 .

2022-11-16 | GSE181350 | GEO

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