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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Pioneer factor FOXA1 defines GATA2- and AR-mediated transcriptional program in prostate cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Jindan Yu

PROVIDER: E-GEOD-69045 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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FOXA1 acts upstream of GATA2 and AR in hormonal regulation of gene expression.

Zhao J C JC Fong K-W KW Jin H-J HJ Yang Y A YA Kim J J Yu J J

Oncogene 20160111 33

Hormonal regulation of gene expression by androgen receptor (AR) is tightly controlled by many transcriptional cofactors, including pioneer factors FOXA1 and GATA2, which, however, exhibit distinct expression patterns and functional roles in prostate cancer. Here, we examined how FOXA1, GATA2 and AR crosstalk and regulate hormone-dependent gene expression in prostate cancer cells. Chromatin immunoprecipitation sequencing analysis revealed that FOXA1 reprograms both AR and GATA2 cistrome by prefe ...[more]

PMID: 26751772

Similar Datasets

Pioneer factor FOXA1 defines GATA2- and AR-mediated transcriptional program in prostate cancer [gene expression]

Project description:AR is tightly regulated by many transcriptional cofactors, including key pioneer factor such as FOXA1 and GATA2. While FOXA1 was recently shown to be able to redistribute AR across the genome, how GATA2 regulates AR cistrome has not been carefully investigated. Here, we report that, unlike FOXA1, GATA2 is unable to reprogram AR, but instead it enhances AR program by inducing AR expression and augmenting AR co-occupancy, thereby acting as a pure AR coactivator, rather than a pioneer factor. On the other hand, AR co-occupancy enhances both GATA2 and FOXA1 binding on the chromatin, forming a positive feedback loop. Importantly, we found that FOXA1 is also capable of reprogramming GATA2 by recruiting GATA2 from GATA motif to FKHD-containing regions, being analogous to its pioneering effect on AR signaling. By contrast, GATA2 simply acts as a co-activator of FOXA1 with a lack of pioneering ability. genetic_modification_design

2016-01-11 | E-GEOD-69044 | biostudies-arrayexpress

Androgen receptor-independent function of FoxA1 in prostate cancer metastasis

Project description:FoxA1 has been shown critical for prostate development and prostate-specific gene expression regulation. In addition to its well-established role as an AR pioneering factor,several studies have recently revealed significant AR binding events in prostate cancer cells with FoxA1 knockdown. Furthermore, the role of FoxA1 itself in prostate cancer has not been carefully examined. Thus, it is important to understand the role of FoxA1 in prostate cancer and how it interacts with AR signaling. To address these questions, we generated engineered LNCaP cells with FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression. We performed microarray analysis of these cells. We performed microarray analysis on LNCaP cells with FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression

2013-04-05 | E-GEOD-37314 | biostudies-arrayexpress

Cooperativity and Equilibrium with FOXA1 Define Androgen Receptor Transcriptional Program [array]

Project description:Previous studies have shown that FOXA1 defines prostatic AR binding events, the underlying mechanisms of which, however, are incompletely understood. To test whether ectopic AR and FOXA1 can activate AR target genes, we performed adenoviral of LacZ, AR, FOXA1 or AR+FOXA1 proteins in DU145 cells, followed by microarray analysis of these cells.

2014-06-02 | E-GEOD-54991 | biostudies-arrayexpress

Gene expression of LNCaP cells grown in 2D cultures and polyethlene glycol-based hydrogels with the presence of synthetic androgen, R1881

Project description:Analysis of LNCaP cell molecular differences and their response to R1881 in 2D and 3D cultures. Androgen regulated genes were differentially expressed between 2D and 3D cultures. These results provide insights into factors that influence the expression of androgen regulated genes In this study, LNCaP cells cultured in tissue culture plastic (2D) and in the hydrogel (3D) were maintained up to 3 days and 24 days respectively in serum containing media before they were androgen-starved for 48 hours. Cells were either treated with 1nM R1881 or continued to be androgen-deprived (without R1881 with 0.008% ethanol) for another 48 hours prior to cell harvest for gene expression analysis. Biological triplicates were prepared for each condition.

2013-02-04 | E-GEOD-33610 | biostudies-arrayexpress

Cooperativity and Equilibrium with FOXA1 Define Androgen Receptor Transcriptional Program

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-02 | E-GEOD-55007 | biostudies-arrayexpress

Gene expression of LNCaP cells grown in polyethlene glycol-based hydrogels alone (monocultures) and grown with human osteoblasts as tissue engineered bone (co-culture) with the presence of synthetic androgen, R1881

Project description:Analysis of LNCaP cell molecular differences in monocultures and in co-cultures in the presence of R1881. Human osteoblast molecular signatures were also identified from the tissue engineered bone monocultures. LNCaP cells molecular profile was altered by co-culturing with human osteoblasts compared to LNCaP monocultures with or without R1881 stimulations. These results provide insights into the behavioral change of LNCaP cells in a bone-like microenvironment. In this study, LNCaP cells cultured in the hydrogel were prepared and co-cultured with or without human osteoblasts (in the form oftissue engineered bone). Similarly, tissue engineered bone monocultures were also prepared 4-6 weeks earlier before co-culturing with the LNCaP cells. These cultures were maintained up to 24 days in RPMI growth media (+10% FBS) before they were androgen-starved for 48 hours. Cells were either treated with 1nM R1881 or continued to be androgen-deprived (without R1881 with 0.008% ethanol) for another 48 hours prior to cell harvest for gene expression analysis. Biological triplicates were prepared for each condition.

2014-05-13 | E-GEOD-44143 | biostudies-arrayexpress

Gene expression profiling of prostate cells with CHD1 knockdown

Project description:Gene expression profiling of prostate tumor cells comparing cells that have CHD1 knockdown by shRNA (RWPE-1, OPCN2) or siRNA (LNCaP) with cells treated with non-targeted control. Prostate cell lines had CHD1 knockdown via shRNA or siRNA were hybridized against cells that were targeted with non-targeting control. OPCN2 and RWPE-1 RNA were dye-swapped in replicate experiments.

2011-12-19 | E-GEOD-33531 | biostudies-arrayexpress

Transcription profiling of human LNCaP cells Androgen-starved treated with gedunin and androgen, androgen alone, or vehicle alone for 24h

Project description:Gedunin is a natural product that affects LNCaP androgen-signalling by 24h; We used microarrays to detail the androgen-responsive program of gene expression affected by gedunin treatment at 24h Experiment Overall Design: LNCaP cells were grown to 50% confluency and deprived of androgen, and subsequently treated with gedunin plus androgen, androgen alone, or vehicle alone for 24h prior to direct Trizol lysis and RNA isolation

2008-06-13 | E-GEOD-5508 | biostudies-arrayexpress

Transcription profiling of human androgen starved LNCaP cells treated with celastrol and androgen, androgen alone, or vehicle alone for 24h

Project description:celastrol is a natural product that affects LNCaP androgen-signalling by 24h; We used microarrays to detail the androgen-responsive program of gene expression affected by celastrol treatment at 24h Experiment Overall Design: LNCaP cells were grown to 50% confluency and deprived of androgen, and subsequently treated with celastrol plus androgen, androgen alone, or vehicle alone for 24h prior to direct Trizol lysis and RNA isolation

2008-11-07 | E-GEOD-5507 | biostudies-arrayexpress

Identification of novel androgen-responsive genes by sequencing of LongSAGE libraries

Project description:Background: The development and maintenance of the prostate is dependent on androgens and the androgen receptor. The androgen pathway continues to be important in prostate cancer. Here, we evaluated the transcriptome of prostate cancer cells in response to androgen using long serial analysis of gene expression (LongSAGE) libraries. Results: There were 131 tags (87 genes) that displayed statistically significant (p=<0.001) differences in expression in response to androgen. Many of the genes identified by LongSAGE (35/87) have not been previously reported to change expression in the direction or sense observed. In regulatory regions of the promoter and/or enhancer regions of some of these genes there are confirmed or potential androgen response elements (AREs). The expression trends of 24 novel genes were validated using quantitative real time-polymerase chain reaction (qRT-PCR). These genes were: ARL6IP5, BLVRB, C19orf48, C1orf122, C6orf66, CAMK2N1, CCNI, DERA, ERRFI1, GLUL, GOLPH3, HM13, HSP90B1, MANEA, NANS, NIPSNAP3A, SLC41A1, SOD1, SVIP, TAOK3, TCP1, TMEM66, USP33, and VTA1. The physiological relevance of these expression trends was evaluated in vivo using the LNCaP Hollow Fibre model. Novel androgen-responsive genes identified here participate in protein synthesis and trafficking, response to oxidative stress, transcription, proliferation, apoptosis, and differentiation. Conclusions: These processes may represent the molecular mechanisms of androgen-dependency of the prostate. Genes that participate in these pathways may be targets for therapies or biomarkers of prostate cancer. There are 2 samples. R1881 is the androgen/test sample. Vehicle is the ethanol/control sample.

2009-10-20 | E-GEOD-18401 | biostudies-arrayexpress

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