Investigating the role of CBFB in breast cancer

Adiba Khan¹, Karen Byth¹, Kirsteen Campbell¹, Sandeep Dhayade²


CBFβ is one of the top 17 most recurrently mutated genes in breast cancer. As a crucial transcriptional co-activator, CBFβ improves the DNA-binding affinity of RUNX proteins and therefore transcription of RUNX target genes. Since RUNX proteins have been previously shown to play context dependent roles in breast cancer and CBFβ is an essential regulator of these proteins, we questioned whether it has a phenotypic consequence in this disease setting. In silico analysis of TCGA data using cBioPortal highlighted how CBFβ undergoes varying alterations depending on the subtype of breast tumours. Interestingly in vivo experiments using a MMTV-PyMT;MMTV-Cre, Cbfβfl/fl mouse model of breast cancer, did not present any overt effects on tumorigenesis. This may be due to the mosaic nature of MMTV-Cre expression in PyMT driven tumours and as such we are testing whether Cbfβ is deleted in these tumours through western blotting alongside incorporating an RFP reporter gene for fluorescence imaging of tumours in vivo. Additionally, we have generated inducible-Cre tumour-derived cell lines (MMTV-PyMT;ROSA-Cre-ERT2;Cbfβfl/fl) and conducted a range of biological assays to determine the effects of acutely removing CBFβ on tumorigenesis ex vivo. Preliminary results show reduced rates of growth in tumour cells lacking CBFβ. Together these results will provide an insight into the context dependent roles of CBFβ in different models of breast cancer.