Conditionalin vivodeletion of LYN kinase has little effect on aBRCA1loss-of-function-associated mammary tumour model

Abstract

AbstractLYN kinase is expressed in BRCA1 loss-of-function-dependent mouse mammary tumours, in the cells of origin of such tumours, and in human breast cancer. Suppressing LYN kinase activity in BRCA1-defective cell lines, as well as inin vitrocultures ofBrca1-null mouse mammary tumours, is deleterious to their growth. Here, we have examined the interaction between LYN kinase and BRCA1 loss-of-function in anin vivomouse mammary tumour model, using conditional knockoutBrca1andLynalleles. Comparison ofBrca1tumour cohorts showed little difference in mammary tumour formation between animals that were wild type, heterozygous or homozygous for the conditionalLynallele, although this was confounded by factors including incompleteLynrecombination in some tumours. RNAseq analysis demonstrated that tumours with high levels ofLyngene expression had a slower doubling time, but this was not correlated with levels of LYN staining in tumour cells themselves. Rather, highLynexpression and slower tumour growth were likely a result of B-cell infiltration. The multifaceted role of LYN means it is likely to present difficulties as a therapeutic target in breast cancer.