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Palbociclib releases the latent differentiation capacity of neuroblastoma cells [RNA-seq PB and RA]

ABSTRACT: We have used RNA-seq to assess the global impact of palbociclib, retinoic acid and the combined treatment on the transcriptome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216274 | GEO | 2023/08/15

REPOSITORIES: GEO

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Palbociclib releases the latent differentiation capacity of neuroblastoma cells [H3K27ac ChIP-seq PB and RA]

Project description:We have used H3K27ac ChIP-seq to assess the global impact of the combination of palbociclib and retinoic acid on the epigenetic H3K27ac landscape in three neuroblastoma cell lines.

2023-08-15 | GSE236052 | GEO

Palbociclib releases the latent differentiation capacity of neuroblastoma cells [RNA-seq PB]

Project description:We have used RNA-seq to assess the global impact of palbociclib on the transcriptome at early and late time points in three neuroblastoma cell lines.

2023-08-15 | GSE216273 | GEO

Palbociclib releases the latent differentiation capacity of neuroblastoma cells [H3K27ac ChIP-seq palbociclib]

Project description:We have used H3K27ac ChIP-seq to assess the global impact of palbociclib on the epigenetic H3K27ac landscape in three neuroblastoma cell lines.

2023-08-15 | GSE216291 | GEO

Palbociclib releases the latent differentiation capacity of neuroblastoma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-15 | GSE216292 | GEO

Transcriptomic expression of A549 and SUM159 cells treated with palbociclib and indisulam

Project description:Indisulam is a molecular glue targeting a splicing factor RBM39 for degradation. To assess splicing errors when treating the cells with indisulam, palbociclib and the combination we perform RNA sequencing and analyze splicing errors.

2022-03-03 | GSE197602 | GEO

Expression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib

Project description:Expression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage) during 5 consecutive days PML plays a role in the senescence tumor suppressor response of normal cells to oncogenic stress. PML also mediates therapy-induced senescence in acute promyelocytic leukemia cells after treatment with retinoic acid. However, many tumor cell lines fail to engage a complete senescence response to PML activation. Interestingly, in vivo and in vitro combination of PML overexpression with CDK inhibition induce senescence in PC3 prostate cancer cells. We used microarray to characterize the gene expression profile of PC3 stably expressing PML or a control vector after subcutaneous injection in BALB/c 6-wk-old nude mice and treatment of the mice with palbociclib (100mg/kg/day) during 5 consecutive days.. PC3 cells were infected with a retroviral vector that express PML or an empty vector before subcutaneous injection of 10^6 cells in both flanks of BALB/c 6-wk-old nude mice. Then, mice were treated for 5 consecutive days with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage)

2016-07-03 | E-GEOD-70923 | biostudies-arrayexpress

Single cell RNA Seq to study the effects of Palbociclib in the mouse LSK cell compartment

Project description:To understand how Palbociclib (a CDK4/6 inhibitor) treatment changes the transcriptome of hematopoietic stem and progenitor cells, wildtype cells were isolated from mice and treated for 24h with either PBS (control) or Palbociclib. After 24h of culture, the cell suspensions were collected and sorted for lineage-negative, Sca1-positive, cKit-positive (LSK) cells which were subjected to library prep for single cell RNA sequencing.

2024-05-22 | E-MTAB-13268 | biostudies-arrayexpress

Gene expression alterations associated with acquired-resistance to the CDK4/6 inhibitor palbociclib [Palbociclib resistance_RNASeq]

Project description:RNA-seq was performed to compare the transcriptional programmes of palbociclib-resistant A375 and CHL1 cells compared to their parental counterparts Cyclin dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor positive breast cancer and are currently in clinical development in melanoma; a tumour that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib, and demonstrated that palbociclib-mediated inhibition of PRMT5 is essential for sensitivity to CDK4/6 inhibitors. Mechanistically, by inhibiting PRMT5 activity, palbociclib alters MDM4 pre-mRNA splicing leading to decreased MDM4 protein expression and subsequent p53 activation. In turn, p53 increases p21 leading to inhibition of CDK2, the main kinase substituting for CDK4/6 and a key driver of resistance to palbociclib. Loss of the ability of palbociclib to regulate the PRMT5-MDM4 axis leads to resistance. Importantly, combining palbociclib with the PRMT5 inhibitor GSK3326595 enhances the efficacy of palbociclib in treatment naïve and resistant models and also delays the emergence of resistance. Our studies have uncovered a novel mechanism of action of CDK4/6 inhibitors in regulating the MDM4 oncogene and the tumor suppressor, p53. Furthermore, we have established that palbociclib inhibition of the PRMT5-MDM4 axis is essential for robust melanoma cell sensitivity and provide pre-clinical evidence that co-inhibition of CDK4/6 and PRMT5 is an effective and well tolerated therapeutic strategy. Overall our data provides a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors in not only melanoma but other tumour types including breast, pancreatic and esophageal carcinoma.

2019-08-23 | GSE133567 | GEO

Gene expression profiles between the palbociclib monotherpy versus palbociclib alternating with ICI182,780 treatment in breast cancer cells at 10 weeks.

Project description:We examined differential gene expression profiles between MCF7 human breast cancer cells treated with vehicle alone (control), palbociclib monotherapy, palbociclib alternating with ICI182,780 treatment, and palbociclib resistant cells. For this, we used gene microarray expression profiling to identify significantly changed genes under different treatment conditions.

2023-04-10 | GSE229002 | GEO

RNA-seq of human breast cancer cell lines MCF7 and T74D naive and resistant to palbociclib treated with capivasertib, fulvestrant and combination

Project description:T47D and MCF7 cell lines were treated with long-term (continuous) palbociclib to induce 4 resistant cell-lines (T47D RB-, T47D CDK6H, MCF7 RB- and MCF7 PacqR). Each cell line (both parental and resistant) were then treated with DMSO (control), capivasertib monotherapy, fulvestrant monotherapy and capivasertib/fulvestrant combination. RNA data is available after each treatment and resistant cell lines additionally have RNA data available after continuous palbociclib treatment.

2023-08-14 | E-MTAB-13262 | biostudies-arrayexpress

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