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ABSTRACT: Transcriptional profile of MCF7 lines sensitive and resistant to Palbociclib

PROVIDER: PRJNA798002 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17643353_1.fastq.gz	Fastqsanger.gz
	SRR17643353_2.fastq.gz	Fastqsanger.gz
	SRR17643354_1.fastq.gz	Fastqsanger.gz
	SRR17643354_2.fastq.gz	Fastqsanger.gz
	SRR17643355_1.fastq.gz	Fastqsanger.gz

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Resistance to Palbociclib requires multiple targetable mechanisms highlighting the potential of drug holidays and drug switching to improve therapeutic outcome

Project description:Estrogen receptor positive (ER+) breast cancer is the most common type of breast cancer. Despite the great efficacy of endocrine therapies, resistance remains a problem. Therefore, there is an immediate need for new, effective therapies in ER+ BC. In this study, we have explored the role of a potent CDK4/6 inhibitor called palbociclib. In order to identify alterations in protein abundance between the responsive and resistant setting, we generated a panel of palbociclib-sensitive and resistant cell lines and did quantitative, shotgun proteomics using dimethyl labelling. Palbociclib sensitive cell lines (wt-MCF7 or MCF7-LTED) were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol or 10% dextran-coated charcoal (DCC) respectively. Thereafter, palbociclib resistant cell lines were generated using 1μΜ palbociclib concentration. Samples were harvested at baseline and at the point of resistance.

2020-03-25 | PXD005611 | Pride

TUMOUR KINOME RE-WIRING GOVERNS RESISTANCE TO PALBOCICLIB IN OESTROGEN RECEPTOR POSITIVE BREAST CANCERS, HIGHLIGHTING NEW THERAPEUTIC MODALITIES

Project description:Estrogen receptor positive (ER+) breast cancers are the most common type of breast cancer. Despite the great efficacy of endocrine therapies, resistance remains a problem. Therefore, there is an immediate need for new, effective therapies in ER+ BC. In this study, we have explored the role of a potent CDK4/6 inhibitor called palbociclib. In order to identify differential phosphoproteomic events that underpin the mode of action and recurrence for this treatment, we generated a panel of palbociclib-sensitive and resistant cell lines and did quantitative, shotgun phosphoproteomics using titanium IMAC. Palbociclib sensitive cell lines (wt-MCF7 or MCF7-LTED) were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol or 10% dextran-coated charcoal (DCC) respectively. Thereafter, palbociclib resistant cell lines were generated using 1μΜ palbociclib concentration. Samples were harvested at baseline and at the point of resistance.

2020-04-29 | PXD005514 | Pride

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

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.

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An increase in oxidative stress downstream of mTORC1 but not AKT causes a proliferative defect in cancer cells with acquired resistance to PI3K/mTOR inhibitors

Project description:Proteomics and phosphoproteomics analysis of MCF7 cells sensitive and resistant to the PI3K inhibitor GDC-0941. The analysis was done for parental and 3 resistant cell lines maintained in the presence or the absence of the drug. One of the resistant cell lines (G2) was also treated with vehicle or the kinase inhibitors GDC0941, MK-2206 and Ku-0063794 for 2h. The proteomics analysis of sensitive and resistant MCF7 cells in basal conditions and phosphoproteomics analysis of the G2 cells in the presence of inhibitors of the PI3K pathway were run in a nano flow ultrahigh pressure liquid chromatography (UPLC, nano Acquity, Waters) coupled to an LTQ-Orbitrap XL mass spectrometer (Thermo Fisher Scientific). The phosphoproteomics study of sensitive and resistant MCF7 cells in basal conditions was run in a Dionex UltiMate 3000 RSLCnano coupled to an Orbitrap Q Exactive Plus mass spectrometer (Thermo Fisher Scientific).

2018-04-09 | PXD003594 | Pride

Promoter methylation data: OHT/ICI-sensitive vs. -resistant cell lines

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Activation of the interferon signaling pathway is associated with resistance to CDK4/6 inhibitors and immune checkpoint activation in ER-positive breast cancer [RNA-seq]

Project description:CDK4/6 inhibitors are highly effective against ER+/HER2- breast cancer (BC); however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6 inhibitors may lead to the identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes. Parental BC cells and their endocrine-resistant derivatives (EndoR) were used in this study. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. We found that parental and EndoR BC lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high Interferon (IFN) signaling and reduced sensitivity to CDK4/6 inhibitors, thus an ‘IFN-Related Palbociclib-Resistance Signature’ (IRPS) was derived. In two neoadjuvant trials of a CDK4/6 inhibitor plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6 inhibition. PalboR derivatives displayed a dramatic activation of IFN/STAT1-signaling compared to their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis. Our study demonstrates that aberrant IFN-signaling is associated with intrinsic resistance to CDK4/6 inhibitors. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN-pathway, which warrants additional studies to clarify its involvement in resistance to CDK4/6 inhibitors.

2021-12-04 | GSE150997 | GEO

TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [4C-seq]

Project description:We report the 4C-Seq profile of the IGFBP3 transcriptional start site in MCF7 and MCF7 TRPS1 CRISPR KO cell lines.

2018-08-07 | GSE107022 | GEO

Gene expression analyses of palbociclib treated ER+ breast cancer cell lines as assessed by RNA-seq

Project description: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.

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Promoter methylation data: OHT/ICI-sensitive vs. -resistant cell lines

Project description:MCF7 breast cancer cell lines: drug-resistant (OHT and ICI) cell lines vs. drug-sensitive (wild type) cell lines. Assessment of association between gene expression and methylation. Two comparisons: OHT-resistant vs. wild type, and ICI-resistant vs. wild type. OHT: 4-hydroxytamoxifen ICI: fulvestrant ((ICI 182780) This submission represents the methylation component of the study.

2011-10-04 | E-GEOD-25519 | biostudies-arrayexpress

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