GEO DataSets

(Submitter supplied) Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

6 Samples

Download data: BED, BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

15 Samples

Download data: BED, BW

(Submitter supplied) We performed SMAD2 ChIP-seq analysis in T47D cells with/without Palbociclib treatment. To validate whether the changes in SMAD2 binding to the genome indeed resulted in changes in target gene expression, we performed RNA-seq transcriptome analyses in T47D with/without ActA stimulation and Palbo treatment.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

4 Samples

Download data: BW, FPKM_TRACKING

(Submitter supplied) Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17303

5 Samples

Download data: BED, BW

(Submitter supplied) Gene expression levels were determined with control or PD-0332991 treatment

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL18573

18 Samples

Download data: CSV

(Submitter supplied) RNA-seq was performed to compare the transcriptional programmes of A375 cells treated with Palbociclib or GSK3326595 compared to untreated cells 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: CSV

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: CSV

(Submitter supplied) The goal of this study is to measure gene expression changes resulting over time of palbociclib treatment of T47D, MCF7, and CAMA1 ER+ breast cancer cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

15 Samples

Download data: XLSX

(Submitter supplied) Transcriptional profiling of breast cell lines comparing breast cell line mixed reference with individual breast cell lines. Goal was to characterize breast cell line subtypes.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL7264

51 Samples

Download data: TXT

(Submitter supplied) Background: Estrogen receptor-positive (ER+) breast cancers represent approximately two-thirds of all breast cancers and have a sustained risk of late disease recurrence. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown significant efficacy in ER+ breast cancer. However, their effects are still limited by drug resistance. In this study, we aim to explore the role of long noncoding RNA TROJAN in ER+ breast cancer. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

3 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome variation profiling by SNP array; SNP genotyping by SNP array

Platforms:

GPL6801 GPL10558

31 Samples

Download data: CEL, CHP

(Submitter supplied) Combination of CDK4/6 inhibitors and endocrine therapy has been shown to improve clinical outcome in advanced estrogen receptor-positive breast cancer. However, not all patients will benefit and relapse is inevitable making the identification of new therapeutic strategies/biomarkers of particular importance.

Organism:

Homo sapiens

Type:

Genome variation profiling by SNP array; SNP genotyping by SNP array

Platform:

GPL6801

8 Samples

Download data: CEL, CHP

(Submitter supplied) Combination of CDK4/6 inhibitors and endocrine therapy has been shown to improve clinical outcome in advanced estrogen receptor-positive breast cancer. However, not all patients will benefit and relapse is inevitable making the identification of new therapeutic strategies/biomarkers of particular importance.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

23 Samples

Download data: TXT

(Submitter supplied) The results from our study have identified two clinically relevant, divergent and druggable pathways (DNA repair and STAT3) that can be targeted in combination to effectively combat drug resistance. We also found that the same pathways that were deregulated in palbociclib-resistant cells were also altered in tumor samples obtained from patients who progressed while on palbociclib and endocrine therapy

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

7 Samples

Download data: XLSX

(Submitter supplied) Purpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

26 Samples

Download data: CEL

(Submitter supplied) Agilent gene expression arrays were used for intrinsic subtyping and to measure changes after anastrozole (C1D1) and after combination of anastrazole and palbociclib (C1D15).

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

118 Samples

Download data: TXT

(Submitter supplied) We have used ChIP-seq to profile binding of the estrogen receptor (ER) to chromatin in response to two mTOR inhibitors, i.e. everolimus (RAD001) and vistusertib (AZD2014). Two hours of treatment with these inhibitors significantly affected mTOR signaling, but surprisingly did not affect binding of ER to chromatin. This suggests that these mTOR inhibitors work through largely ER-independent mechanisms.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

24 Samples

Download data: NARROWPEAK

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

51 Samples

Download data: CEL

(Submitter supplied) Cyclin D-CDK4/6 are the first CDK complexes to be activated in G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (Palbociclib) was recently approved by the FDA to treat advanced ER+ breast tumors. Unfortunately, reliable predictive tools are lacking to identify potentially responsive or insensitive tumors. We have shown that the activating T172 phosphorylation of CDK4 is the central rate-limiting event that initiates the cell cycle decision and signals the presence of active CDK4. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

31 Samples

Download data: CEL