Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Determinants of response to BLU-222, a potent and highly selective CDK2 inhibitor, in CCNE1-aberrant ovarian and endometrial tumors

ABSTRACT: To further refine our understanding of BLU-222 response in the context of CCNE1, Rb, and p16 expression, we analyzed BLU-222 induced gene expression changes in 18 ovarian cancer cell lines. This panel of responders (GI50 ≤200 nM) and non-responders (GI50 >200 nM) included CCNE1-amplified, CCNE1 CN-increased, and CCNE1-normal cell lines. Each cell line was treated with BLU-222 at its proliferative GI50 and differential mRNA expression analysis between BLU-222 treated cells and DMSO treated cells was performed for each cell line to calculate mRNA expression fold change and identify significantly differentially expressed genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282041 | GEO | 2025/01/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CCNE1 interactome analysis in HEK293T cells under the treatment of different CCNE1(:CDK2) ligands

Project description:This is to explore potential functional effects of CCNE1(:CDK2) ligands and compare them side by side.

2024-09-03 | PXD048328 | Pride

222

Project description:222

| PRJEB34284 | ENA

Determinants of response to BLU-222, a potent and highly selective CDK2 inhibitor, in CCNE1-aberrant ovarian and endometrial tumors

Project description:Determinants of response to BLU-222, a potent and highly selective CDK2 inhibitor, in CCNE1-aberrant ovarian and endometrial tumors

| PRJNA1186705 | ENA

Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells

2011-01-29 | GSE19777 | GEO

Differential responses to selective CDK2 inhibitor BLU-222 is conditioned by tumor suppressors

Project description:The selective CDK2 inhibitor BLU-222 was evaluated for mechanisms of response in the context of ovarian and breast cancer models. Using sensors of cellular CDK activity, it was found that sensitivity to either CDK4/6 or CDK2 inhibition is related to the differential dependence on a single CDK for G1/S transition. Unlike CDK4/6 inhibitors, BLU-222 was able to robustly inhibit proliferation through cell cycle inhibition in both G1 and G2 phases. However, it remained possible for cells to re-enter the cell cycle upon drug withdrawal. The anti-proliferative strength and impact on G1/S versus G2/M accumulation was found to be mediated by the RB tumor suppressor, as determined by functional perturbation strategies. To broaden the sensitivity to CDK2 inhibition, combinatorial drug screens were performed that identified both synergistic (e.g., CDK4/6 inhibitors) and antagonistic (e.g., WEE1 inhibitors) relationships. Models that were exceptionally sensitive to CDK2 inhibition displayed coordinate expression of Cyclin E1 and P16INK4A, an endogenous CDK4/6 inhibitor. Functional studies demonstrated that P16INK4A and CDK4/6 activity were key mediators of sensitivity to BLU-222. Clinical gene and protein expression analysis revealed a positive correlation between Cyclin E1 and P16INK4A and that ~25% of ovarian cancers exhibited coordinate expression of Cyclin E, P16INK4A, and RB, indicative of strong sensitivity to CDK2 inhibition. Together, this work advances a precision strategy for the use of CDK2 inhibitors in the context of ovarian and breast cancers.

2024-12-22 | GSE281746 | GEO

Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells

Project description:Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment. Fulvestrant-resistant breast cancer cells MCF7-FR (originated from drug-sentitive breast cancer model cell line MCF7) were transient-transfected by antigomirs targeting miR221 or miR222 (i.e. si221, si222). All three cell lines, MCF7-FR, siR221, siRNA222 were subjected to gene expression profiling.

2011-01-29 | E-GEOD-19777 | biostudies-arrayexpress

Transcriptional adaptation to DNA replication stress induced by CCNE1 overexpression

Project description:We overproduced human cyclin E from a stably-integrated inducible CCNE1 transgene in RPE1-hTERT cells over a period of weeks. CCNE1 overproduction induced replication stress, then slow proliferation, followed by adaptation to normal growth phenotype. We analyzed mRNA transcripts at key points of the timecourse: control, 2 days, 15-18 days, 39-51 days, and at a point several weeks after induction was withdrawn

2021-10-01 | GSE171845 | GEO

Transcriptional profilng of CCNE1 overexpressing hTERT-immortalized p53-R175H fallopian tube cell lines (FT282)

Project description:In this study we used RNA-seq to profile transcriptional changes in two clones of FT282-hTERT p53-R175H cells engineered to overexpress CCNE1. We compared the differential gene expression (DGE) of CCNE1 OE to their wild type counterparts and identified that CCNE1 OE increases expression of genes involved in G2/M progression. Subsequent gene set enrichment analysis (GSEA) revealed significant enrichment of genes co-regulated by MYBL2 and FOXM1 transcription factors.

2022-02-15 | GSE171453 | GEO

Bradyrhizobium yuanmingense strain:USDA 222 | isolate:USDA 222

Project description:Bradyrhizobium yuanmingense USDA 222 genome sequencing

| PRJNA1115314 | ENA

Gene expression profiling of MCF10A (miR-221/222 vs control)

Project description:Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222

2011-06-14 | GSE29327 | GEO