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The SRC-family kinase LYN acts as a tumour suppressor gene in an in vivo BRCA1 loss-of-function-associated mammary tumourigenesis model

ABSTRACT: To examine the interaction between LYN kinase and BRCA1 loss-of-function in an in vivo mouse mammary tumour model, we have used conditional knockout Brca1 and Lyn alleles targeted to the mammary epithelium, on a p53 heterozygote background. Comparison of tumour cohorts demonstrated that homozygous conditional Lyn cohorts developed tumours significantly faster than the other genotypes. Transcriptomic analysis to identify and compare tumours with the highest and lowest Lyn levels from across the cohorts showed that ‘Lyn high’ tumours had a significantly slower doubling time and were enriched in inflammatory pathways and canonical NfkB signalling. ‘Lyn low’ tumours had a faster doubling time and were enriched in PI3K, WNT and NOTCH pathways. Therefore, these results suggest that, in this model at least, LYN acts as a tumour suppressor in the context of Brca1 loss.

ORGANISM(S): Mus musculus

PROVIDER: GSE222075 | GEO | 2023/01/23

REPOSITORIES: GEO

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Transcription profiling by array of mouse mammary epithelial stem cell tumours.

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