Proteomics

Dataset Information

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


ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: GSE98987GSE99003

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Anna Ressa  

LAB HEAD: Dr Lesley-Ann Martin

PROVIDER: PXD005514 | Pride | 2020-04-29

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MCF7_A1_wt_IMAC_1.raw Raw
MCF7_A1_wt_IMAC_2.raw Raw
MCF7_A1_wt_IMAC_3.raw Raw
MCF7_A2_wt_IMAC_1.raw Raw
MCF7_A2_wt_IMAC_2.raw Raw
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Publications


Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss of RB1 few gene-copy number (CN) alterations are associated with irreversible-resistance to endocrine therapy and subsequent secondary resistance to palbociclib. Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression of EGFR, M  ...[more]

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