Regulation of the interferon-gamma (IFN-γ) pathway by p63 and Δ133p53 isoform in different breast cancer subtypes

Oncotarget
Sunali Y MehtaAntony W Braithwaite

Abstract

The TP53 family consists of three sets of transcription factor genes, TP53, TP63 and TP73, each of which expresses multiple RNA variants and protein isoforms. Of these, TP53 is mutated in 25-30% of breast cancers. How TP53 mutations affect the interaction of TP53 family members and their isoforms in breast cancer is unknown. To investigate this, 3 independent breast cancer cohorts were stratified into 4 groups based on oestrogen receptor (ER) and TP53 mutation status. Using bioinformatic methodologies, principal signalling pathways associated with the expression of TP53 family members were identified. Results show an enrichment of IFN-γ signalling associated with TP63 RNA in wild type TP53 (wtTP53), ER negative (ER-) tumours and with Δ133TP53 RNA in mutant TP53 (mTP53) ER positive (ER+) tumours. Moreover, tumours with low IFN-γ signalling were associated with significantly poorer patient outcome. The predicted changes in expression of a subset of RNAs involved in IFN-γ signalling were confirmed in vitro. Our data show that different members of the TP53 family can drive transcription of genes involved in IFN-γ signalling in different breast cancer subgroups.

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Citations

Aug 23, 2019·Cell Death & Disease·Marina KazantsevaAntony W Braithwaite
Feb 15, 2021·Experimental and Molecular Pathology·Ali SattariMohammad Taheri
Nov 16, 2021·EMBO Reports·Sunali MehtaAntony W Braithwaite

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Datasets Mentioned

BETA
GSE3494
GSE61725

Methods Mentioned

BETA
transfection
co-immunoprecipitation
RNA-seq
transfections
electrophoresis
PCR

Software Mentioned

PANTHER
cBioPortal
R
Venny

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