Dataset Information

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

ABSTRACT: 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).

INSTRUMENT(S): LTQ Orbitrap, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Pedro Casado-Izquierdo

LAB HEAD: Pedro R. Cutillas

PROVIDER: PXD003594 | Pride | 2018-04-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	F001608.dat-pride.xml-merged.pride.mgf.gz	Mgf
	F001608.dat-pride.xml-merged.pride.mztab.gz	Mztab
	F001608.dat-pride.xml-merged.xml.gz	Xml
	F002356.dat-pride.xml-merged.pride.mgf.gz	Mgf
	F002356.dat-pride.xml-merged.pride.mztab.gz	Mztab

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Oxidative stress downstream of mTORC1 but not AKT causes a proliferative defect in cancer cells resistant to PI3K inhibition.

Dermit M M Casado P P Rajeeve V V Wilkes E H EH Foxler D E DE Campbell H H Critchlow S S Sharp T V TV Gribben J G JG Unwin R R Cutillas P R PR

Oncogene 20161219 19

Compounds targeting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling are being investigated in multiple clinical settings, but drug resistance may reduce their benefit. Compound rechallenge after drug holidays can overcome such resistance, yet little is known about the impact of drug holidays on cell biochemistry. We found that PI3K inhibitor (PI3Ki)-resistant cells cultured in the absence of PI3Ki developed a proliferative defect, increased oxygen consumption an ...[more]

PMID: 27991931

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