RNA sequencing of LNCaP cells treated with castration and/or enzalutamide
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE202755 | GEO | 2022/05/12
REPOSITORIES: GEO
Similar Datasets
Project description:We generated and characterized an androgen-independent LNCaP-AI cell line by long-term culture of androgen-dependent LNCaP cells in RPMI-1640 medium containing charcoal-stripped serum. This approach used to generate the line mimics the castration resistant condition for treating prostate cancer, supporting the relevance of the LNCAP-AI cell line to Castration Resistant Prostate Cancer.
2019-01-01 | GSE124519 | GEO
Project description:Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent. Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival.
2016-12-14 | GSE92347 | GEO
Project description:Building on the observation that metastatic, castration-resistant prostate cancer (CRPC) correlates with activation of Src-family tyrosine kinases, we showed that the expression of activated Src renders LNCaP androgen-independent. Here, we report on RNA-seq and/or AR ChIP-seq analyses of LNCaP, LNCaP[Src], VCaP, 22Rv1 cells grown in the presence or absence of 10 nM DHT for 16h, or LuCaP35.1 tumors grown in androgen-supplemented vs. castrated mice (androgen-dependent vs. castration-resistant). We identify an 11-gene Src-induced signature found only in CRPC in response to DHT, and moreover, the differentail expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival.
2016-12-20 | GSE92574 | GEO
Project description:This a model from the article:
Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats.
Potter LK, Zager MG, Barton HA. Am J Physiol Endocrinol Metab.
2006:91(5):E952-64. 16757547
,
Abstract:
The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. Understanding these regulatory mechanisms is important for assessing the reproductive effects of environmental and pharmaceutical androgenic and antiandrogenic compounds. A mathematical model for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the adult rodent ventral prostate was developed on the basis of a model by Barton and Anderson (1997). The model describes the systemic and local kinetics of testosterone (T), 5alpha-dihydrotestosterone (DHT), and luteinizing hormone (LH), with metabolism of T to DHT by 5alpha-reductase in liver and prostate. Also included are feedback loops for the positive regulation of T synthesis by LH and negative regulation of LH by T and DHT. The model simulates maintenance of the prostate as a function of hormone concentrations and androgen receptor (AR)-mediated signal transduction. The regulatory processes involved in prostate size and function include cell proliferation, apoptosis, fluid production, and 5alpha-reductase activity. Each process is controlled through the occupancy of a representative gene by androgen-AR dimers. The model simulates prostate dynamics for intact, castrated, and intravenous T-injected rats. After calibration, the model accurately captures the castration-induced regression of the prostate compared with experimental data that show that the prostate regresses to approximately 17 and 5% of its intact weight at 14 and 30 days postcastration, respectively. The model also accurately predicts serum T and AR levels following castration compared with data. This model provides a framework for quantifying the kinetics and effects of environmental and pharmaceutical endocrine active compounds on the prostate.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Potter, Zager, Barton (2006) - version03
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL8684444027 | BioModels
Project description:Inhibition of the androgen receptor (AR) by anti-androgens is the standard treatment for castration resistant prostate cancer (CRPC), but it inevitably leads to the development of resistance. We generated two multi anti-androgen resistant cell-line models by treatment of LNCaP cells with enzalutamide (ResA) and RD-162 (ResB). Both cell-lines have an AR independent, non-neuroendocrine phenotype. To identify the resistance mechanisms we performed RNASeq analysis. To this end, the three cell-lines were plated in medium with 5% dextran-coated charcoal (DCC) treated FCS at a density of 1 million cells/well in 6-well plates. After 24 hours of steroid starvation the cells were treated with 10 nM of the androgen dihydrotestosterone (DHT), 10 µM of the anti-androgen enzalutamide, a combination of the two, or vehicle (DMSO) for 18 hours.
2019-09-26 | GSE130534 | GEO
Project description:Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA. Here we used Affymetrix human genome microarray technology to investigate the global programme of gene expression of LNCaP cells in response to enzalutamide alone and in the context of DHT-stimulated androgen receptor gene expression. LNCaP cells were grown in RPMI 1640 supplemented with 5% hormone depleted FBS and treated with vehicle (control sample) , DHT (100 nM), enzalutamide (1 or 10 M-BM-5M) or DHT (100 nM) plus enzalutamide (1 or 10 M-BM-5M)for 16 hours for RNA extraction and hybridization. Each condition was done in triplicate.
2013-04-01 | E-GEOD-44905 | biostudies-arrayexpress
Project description:It has been well established that the transcription factor androgen receptor (AR) is obligatory for prostate cancer (PCa) development and progression, but the precise role of the AR in these processes is still unclear. To dissect the role of AR in shaping the transcriptome of prostate cancer cells, RNA-seq data were obtained from AR-positive LNCaP cells treated with various regimens to manipulate endogenous AR signaling. LNCaP cells were cultured in normal medium containing fetal bovine serum (FBS) to represent an androgen-dependent (AD) growth state. To mimic the clinical androgen-deprivation-therapy (ADT) settings, cells were grown for 4 days in conditions of either depletion of androgen (i.e., medium containing charcoal:dextran stripped fetal bovine serum (CDSS)) or the presence of AR antagonist Enzalutamide (MDV3100, 10 μM) to represent androgen-independent (AI) growth states. Aside from the pharmaceutical modulations, we also utilized siRNA to knockdown AR. To examine the direct effects of AR signaling on gene transcription and splicing, cells were primed with CDSS for 3 days followed by treatment of 10nM dihydrotestosterone (DHT) for 8-9 hrs. Deep sequencing of rRNA-depleted total RNAs was performed in biological duplicates on abovementioned LNCaP cultures.
2020-03-04 | GSE114052 | GEO
Project description:To further determine the gene expression in the castration resistant condition for treating PCa, we generated and characterized an androgen-independent LNCaP-AI cell line by long-term culture of androgen-dependent LNCaP cells in RPMI-1640 medium containing charcoal-stripped serum.
2018-12-22 | GSE124291 | GEO
Project description:Metastatic prostate cancer is commonly localized in bone and treated with androgen ablation, which is initially highly effective, but eventually results in resistant cancer cells. The decreased dependence on androgen is associated with activation of the androgen receptor (AR) via other growth factor receptor pathways. The current study analyzed global gene expression in bone from castrated and sham operated C57BL/6 mice to identify factors that may be responsible for androgen signaling. Androgen suppression by castration increased the expression of 159 genes with insulin-like growth factor binding protein 5 (IGFBP5) being the most consistently increased. IGFBP5 protein was detected by immune histochemistry in osteoblasts, bone marrow stromal cells and endothelial cells. In vitro treatment of marrow stromal cells with charcoal-stripped serum increased IGFBP5 mRNA expression approximately 25-fold and was reversed by androgen supplementation. Endogenous IGFBP5 was incorporated into extracellular matrix. In addition, treatment of extracellular matrices with exogenous IGFBP5 and IGF-1 or IGF-2 enhanced the growth of immortalized human prostate cells. These results suggest that androgen ablative therapy may increase IGFBP5 in the marrow microenvironment, thereby providing support for the development of therapy resistance prostate cancer cells. Keywords: Bone Marrow Environment, Androgen Suppression, IGFBP5, prostate cancer
2007-06-01 | GSE5776 | GEO
Project description:Metastatic prostate cancer is commonly localized in bone and treated with androgen ablation, which is initially highly effective, but eventually results in resistant cancer cells. The decreased dependence on androgen is associated with activation of the androgen receptor (AR) via other growth factor receptor pathways. The current study analyzed global gene expression in bone from castrated and sham operated C57BL/6 mice to identify factors that may be responsible for androgen signaling. Androgen suppression by castration increased the expression of 159 genes with insulin-like growth factor binding protein 5 (IGFBP5) being the most consistently increased. IGFBP5 protein was detected by immune histochemistry in osteoblasts, bone marrow stromal cells and endothelial cells. In vitro treatment of marrow stromal cells with charcoal-stripped serum increased IGFBP5 mRNA expression approximately 25-fold and was reversed by androgen supplementation. Endogenous IGFBP5 was incorporated into extracellular matrix. In addition, treatment of extracellular matrices with exogenous IGFBP5 and IGF-1 or IGF-2 enhanced the growth of immortalized human prostate cells. These results suggest that androgen ablative therapy may increase IGFBP5 in the marrow microenvironment, thereby providing support for the development of therapy resistance prostate cancer cells. Keywords: Bone Marrow Environment, Androgen Suppression, IGFBP5, prostate cancer
2007-06-01 | GSE5775 | GEO