Stable overexpression of MED19 in androgen-dependent LNCaP cells promotes growth under conditions of androgen deprivation
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ABSTRACT:
PROVIDER: PRJNA676106 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13017706.fastq.gz | Fastqsanger.gz | |||
| SRR13017707.fastq.gz | Fastqsanger.gz | |||
| SRR13017708.fastq.gz | Fastqsanger.gz | |||
| SRR13017709.fastq.gz | Fastqsanger.gz | |||
| SRR13017710.fastq.gz | Fastqsanger.gz |
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Project description:We report the application of ChIP and RNA sequencing to identify the mechanism whereby stable overexpression of MED19 in androgen-dependent LNCaP cells promotes growth under conditions of androgen deprivation. We determined the MED19 and AR transcriptomes and cistromes in control and MED19 LNCaP cells. We also examined genome-wide H3K27 acetylation in both the absence and presence of androgens. We found that MED19 overexpression selectively alters AR occupancy, H3K27 acetylation, and gene expression. Under conditions of androgen deprivation, genes regulated by MED19 correspond to genes regulated by ELK1, a transcription factor that binds the AR N-terminus to induce select AR target gene expression and proliferation. This study provides important insight into the mechanisms of prostate cancer cell growth under low androgen, and underscores the importance of the MED19 in this process.
2021-01-20 | GSE161170 | GEO
Project description:We report the application of RNA sequencing to uncover the process through which sustained overexpression of the canonical MED19 isoform in androgen-dependent LNCaP cells enhances growth under conditions of androgen deprivation. We identified the canonical MED19 transcriptome by comparing control LNCaP cells with those expressing canonical MED19. This research offers significant understanding of the mechanism by which prostate cancer cells grow under low androgen conditions, emphasizing the key role of the canonical MED19 isoform in this process.
2023-07-06 | GSE236441 | GEO
Project description:We report the application of ChIP and RNA sequencing to identify the mechanism whereby stable overexpression of MED19 in androgen-dependent LNCaP cells promotes growth under conditions of androgen deprivation. We determined the MED19 and AR transcriptomes and cistromes in control and MED19 LNCaP cells. We also examined genome-wide H3K27 acetylation in both the absence and presence of androgens. We found that MED19 overexpression selectively alters AR occupancy, H3K27 acetylation, and gene expression. Under conditions of androgen deprivation, genes regulated by MED19 correspond to genes regulated by ELK1, a transcription factor that binds the AR N-terminus to induce select AR target gene expression and proliferation. This study provides important insight into the mechanisms of prostate cancer cell growth under low androgen, and underscores the importance of the MED19 in this process.
2021-01-20 | GSE161167 | GEO
Project description:Transcriptome profiles of alternative MED19 LNCaP and control LNCaP cells cultured under androgen deprivation with vehicle or R1881
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Project description:Transcriptome profiles of canonical MED19 LNCaP and control LNCaP cells cultured under androgen deprivation with vehicle or R1881 treatment
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Project description:The androgen receptor (AR) is a mediator of both androgen-dependent and castration- resistant prostate cancers. Identification of cellular factors affecting AR transcriptional activity could in principle yield new targets that reduce AR activity and combat prostate cancer, yet a comprehensive analysis of the genes required for AR-dependent transcriptional activity has not been determined. Using an unbiased genetic approach that takes advantage of the evolutionary conservation of AR signaling, we have conducted a genome-wide RNAi screen in Drosophila cells for genes required for AR transcriptional activity and applied the results to human prostate cancer cells. We identified 45 AR-regulators, which include known pathway components and genes with functions not previously linked to AR regulation, such as HIPK2 (a protein kinase) and MED19 (a subunit of the Mediator complex). Depletion of HIPK2 and MED19 in human prostate cancer cells decreased AR target gene expression and, importantly, reduced the proliferation of androgen-dependent and castration-resistant prostate cancer cells. We also systematically analyzed additional Mediator subunits and uncovered a small subset of Mediator subunits that interpret AR signaling and affect AR-dependent transcription and prostate cancer cell proliferation. Importantly, targeting of HIPK2 by an FDA approved kinase inhibitor phenocopied the effect of depletion by RNAi and reduced the growth of AR-positive, but not AR negative, treatment-resistant prostate cancer cells. Thus, our screen has yielded new AR regulators including drugable targets that reduce the proliferation of castration-resistant prostate cancer cells. HIPK2 and MED19 were identified via a genome-wide RNAi screen as new androgen receptor (AR) reulators. Our goal in performing this microarray was to identify the gene regulated by HIPK2 and MED19 in a late stage prostate cancer cell line (LNCaP-abl), and to see what genes are in common with known genes to be regulated by AR, and what genes are unique to HIPK2 or MED19. Knockdown of HIPK2 and MED19 was tested in LNCaP-abl cells against control. Each was performed in duplicates. Six samples were analyzed
2013-01-30 | E-GEOD-43881 | biostudies-arrayexpress
Project description:Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Experiment Overall Design: To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI).
2008-04-07 | E-GEOD-8702 | biostudies-arrayexpress
Project description:The androgen receptor (AR) is a mediator of both androgen-dependent and castration- resistant prostate cancers. Identification of cellular factors affecting AR transcriptional activity could in principle yield new targets that reduce AR activity and combat prostate cancer, yet a comprehensive analysis of the genes required for AR-dependent transcriptional activity has not been determined. Using an unbiased genetic approach that takes advantage of the evolutionary conservation of AR signaling, we have conducted a genome-wide RNAi screen in Drosophila cells for genes required for AR transcriptional activity and applied the results to human prostate cancer cells. We identified 45 AR-regulators, which include known pathway components and genes with functions not previously linked to AR regulation, such as HIPK2 (a protein kinase) and MED19 (a subunit of the Mediator complex). Depletion of HIPK2 and MED19 in human prostate cancer cells decreased AR target gene expression and, importantly, reduced the proliferation of androgen-dependent and castration-resistant prostate cancer cells. We also systematically analyzed additional Mediator subunits and uncovered a small subset of Mediator subunits that interpret AR signaling and affect AR-dependent transcription and prostate cancer cell proliferation. Importantly, targeting of HIPK2 by an FDA approved kinase inhibitor phenocopied the effect of depletion by RNAi and reduced the growth of AR-positive, but not AR negative, treatment-resistant prostate cancer cells. Thus, our screen has yielded new AR regulators including drugable targets that reduce the proliferation of castration-resistant prostate cancer cells. HIPK2 and MED19 were identified via a genome-wide RNAi screen as new androgen receptor (AR) reulators. Our goal in performing this microarray was to identify the gene regulated by HIPK2 and MED19 in a late stage prostate cancer cell line (LNCaP-abl), and to see what genes are in common with known genes to be regulated by AR, and what genes are unique to HIPK2 or MED19.
2013-01-30 | GSE43881 | GEO
Project description:Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) was conducted to examine interactome of androgen receptor (AR) in LNCaP cells.
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