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Chromatin targets of androgen receptor and coregulator PIAS1 in molecular apocrine breast cancer cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

OTHER RELATED OMICS DATASETS IN: PRJNA287765

ORGANISM(S): Homo sapiens

PROVIDER: GSE70163 | GEO | 2016/07/18

SECONDARY ACCESSION(S): PRJNA287761

REPOSITORIES: GEO

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SUMO ligase PIAS1 functions as a target gene selective androgen receptor coregulator on prostate cancer cell chromatin.

Project description: Not available

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Chromatin targets of androgen receptor and coregulator PIAS1 in molecular apocrine breast cancer cells

Project description:Chromatin targets of androgen receptor and coregulator PIAS1 in molecular apocrine breast cancer cells

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Chromatin targets of androgen receptor and PIAS1 in molecular apocrine breast cancer cells [ChIP-seq]

Project description:The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor a (ERa). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERa negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells.

2016-07-18 | GSE70161 | GEO

PIAS1 is a target gene selective androgen receptor coregulator in prostate cancer cell chromatin

Project description:To study the importance of PIAS1 (protein inhibitor of activated STAT1) for the androgen-regulated transcriptome of VCaP prostate cancer cells, we silenced its expression by RNAi. Transcriptome analyses revealed that a subset of the androgen-regulated genes is significantly influenced, either activated or repressed, by PIAS1 depletion. The depletion also exposed a completely new set of genes to androgen regulation, suggesting that PIAS1 can mask genes from androgen receptor (AR). Pathway analyses of gene expression data suggest involvement of PIAS1 in VCaP cell proliferation. According to genome-wide ChIP-seq analyses, PIAS1 interacts with the AR on chromatin harboring also SUMO2/3, as androgen exposure multiplied the occupancy of PIAS1 in the chromatin, and resulted in nearly complete overlap with AR chromatin binding events. PIAS1 interacted also with pioneer factor FOXA1 in the chromatin. Our results strongly suggest that PIAS1 is a genuine chromatin-bound coregulator of AR which functions in a target gene selective fashion in prostate cancer cells.

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Molecular Analysis of Luminal Androgen Receptor Reveals Activated Pathways and Potential Therapeutic Targets in Breast Cancer.

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