Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells (mRNA)

ABSTRACT: We report the androgen receptor recruitment to the chromatin of androgen responsive prostate cancer cell lines, LNCaP-1F5 and VCaP in response to physiological androgen 5a-dihydrotestosterone (DHT) using ChIP-sequencing. We compare the AR recruitment by DHT to that by partial agonist/antagonist cyproterone acetate and mifepristone (RU486) in LNCaP-1F5 cells. We also report the role of glucocorticoid receptor recruitment in presence of dexamethasone (Dex) in androgen responsive prostate cancer cells. The AR and GR cistrome analysis is subsequently compared with gene expression data and RNA Pol II analysis. The ChIP-seq has been performed using AR, GR, RNA Pol II antibodies. Expression profiling by microarray of LNCaP-1F5 cells treated with vehicle, 100 nM 5a-dihydrotestosterone (DHT), 100 nM dexamethasone (Dex), 1000 nM cyproterone acetate (CPA), 100 nM mifepristone (RU486) and combination of 100 nM DHT,100 nM Dex for 24 hours.

ORGANISM(S): Homo sapiens

SUBMITTER: Olli Jänne

PROVIDER: E-GEOD-39654 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells.

Sahu Biswajyoti B Laakso Marko M Pihlajamaa Päivi P Ovaska Kristian K Sinielnikov Ievgenii I Hautaniemi Sampsa S Jänne Olli A OA

Cancer research 20121226 5

The forkhead protein FoxA1 has functions other than a pioneer factor, in that its depletion brings about a significant redistribution in the androgen receptor (AR) and glucocorticoid receptor (GR) cistromes. In this study, we found a novel function for FoxA1 in defining the cell-type specificity of AR- and GR-binding events in a distinct fashion, namely, for AR in LNCaP-1F5 cells and for GR in VCaP cells. We also found different, cell-type and receptor-specific compilations of cis-elements enric ...[more]

PMID: 23269278

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Project description:To better assess the impact of contaminants on fish reproduction, it is increasingly important to collect data at multiple levels of biological organization. However, a challenge in ecotoxicology is that three of the most commonly measured reproductive endpoints; gonad histology, ex vivo steroid production, and gene expression, can be difficult to obtain in small-bodied fish (e.g. zebrafish, Japanese medaka, fathead minnow) due to limited tissue availability. Using 5M-NM-1-dihydrotestosterone (DHT) as a test compound, the objectives of the current study were to assess the feasibility of measuring gene expression in tissues also used for ex vivo steroid production studies. A portion of the testes was also used for qualitative histological examination. Male mummichog were exposed to 0, 5, and 50 M-BM-5g/L DHT for 21 days. Following the exposure, testes were collected and separated into three pieces for histology, ex vivo incubation to measure steroidogenic capacity [Testosterone(T), 17M-NM-2-estradiol (E2), 11-ketotestosterone (11KT)] and gene expression analyses. Testis RNA at time of dissection and testis RNA at end of ex vivo incubation (18 h) was collected and assessed for RNA integrity. The expression of genes coding for estrogen receptor M-NM-2a (esrba) and estrogen receptor M-NM-2b (esrbb) as well as the key steroidogenic genes, steroidogenic acute regulatory protein (star), P450 side chain cleavage (p450scc) and 11M-NM-2-hydroxysteroid dehydrogenase (hsd11b3) were assessed in testis before and after ex vivo incubation. There were no significant differences in RNA quality between the two time points, however the expression of esrba, esrbb and p450scc was significantly lower post-incubation, although star, hsd11b3, and all four reference gene expression levels remained unchanged over time. DHT did not affect the expression of any of the measured genes at either concentration. Histological examination showed that all fish contained mature testes dominated by spermatozoa and spermatids. DHT did not affect T production but significantly decreased 11KT production in the high treatment group. This suggests a role for DHT in androgen regulation, and has Microarray analysis was performed with four biological replicates (4 control and 4 treatment). Male mummichog were exposed to 0, 5, and 50 M-BM-5g/L DHT for 21 days. Individuals from the high concentration, 50 ug/L DHT, were used for the microarray analysis.

Dataset Information

FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells (mRNA)

Publications

FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells.

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