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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Runx1 and Runx2 act in concert to suppress Wnt/b-catenin-driven mammary tumourigenesis impacting on mammary stemness and the immune microenvironment

ABSTRACT: The genes for transcription factor RUNX1 and its binding partner CBFb have been reported to be mutated in human breast cancer. We show for the first time that loss of Runx1 in a genetically engineered mouse model results in accelerated disease onset and tumour development aligning RUNX1 as a tumour suppressor in breast cancer. Combined deletion of Runx1 and the related family member Runx2 resulted in mammary epithelial cells becoming exquisitely sensitive to WNT-driven transformation with the emergence of multiple tumours early in life. Clonogenic assays indicated that Runx1 ablation induced a stem cell like phenotype in mammary epithelial cells whilst transcriptome analysis demonstrated activation of multiple oncogenic pathways, especially when Runx2 was co-deleted. While loss of Runx2 itself did not result in tumour promotion we observed dramatic effects when both Runx2 and Runx1 were deleted. Significantly, altered Runx expression in the mammary epithelium also drove profound alterations in the tumour microenvironment impacting the immune landscape revealing extrinsic effects of Runx gene deletion in mammary tissue. Tissue, mouse model: Cell preparations from 9-week mammary glands were from female mice of the following genotypes: 1) BLG-Cre;Catnbwt/lox(ex3) 2) BLG-Cre;Catnbwt/lox(ex3);Runx1fl/fl 3) BLG-Cre;Catnbwt/lox(ex3);Runx2fl/fl 4) BLG-Cre;Catnbwt/lox(ex3); Runx1fl/fl;Runx2fl/fl

INSTRUMENT(S): D1000 ScreenTape Analysis, Qubit Fluorometer., NextSeq 500

ORGANISM(S): Mus musculus

SUBMITTER: Robin Shaw

PROVIDER: E-MTAB-15078 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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