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dc.contributor.authorTahiri, Andliena
dc.contributor.authorTekpli, Xavier
dc.contributor.authorSomisetty, Venkata Satheesh
dc.contributor.authorDeWijn, Rik
dc.contributor.authorLuders, Torben
dc.contributor.authorBukholm, Ida Rashida Khan
dc.contributor.authorHurtado, Antoni
dc.contributor.authorGeisler, Jürgen
dc.contributor.authorKristensen, Vessela N.
dc.identifier.citationBreast Cancer Research and Treatment. 2020, 183, 585-598.en_US
dc.description.abstractPurpose The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2. Experimental design Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR. Results In ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2−. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identified as responsible for the differential phosphorylation between PR− and PR+ in ER+/HER2− tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2− breast cancers. Twenty four kinase-encoding genes were identified as differentially expressed between PR+ and PR−, dividing ER+/HER2− samples in two distinct clusters with significant differences in survival (p < 0.05). Four kinase genes, LCK, FRK, FGFR4, and MST1R, were identified as potential direct targets of PR. Conclusions Our results suggest that the PR status has a profound effect on tyrosine kinases, especially for FGFR4 and LCK genes, in ER+/HER2− breast cancer patients. The influence of these genes on the PI3K/AKT signaling pathway may potentially lead to novel drug targets for ER+/PR− breast cancer patients.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleLoss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast canceren_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalBreast Cancer Research and Treatmenten_US
dc.relation.projectHelse Sør-Øst RHF: 2719014en_US

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal