Poster Presentation 25th Lorne Cancer Conference 2013

Identification of microRNAs that function downstream of Brca1 (#340)

Gurveen Sandhu 1 , Anna Wronski 1 , Juliet French 1 , Brooke Brewster 1 , Stacey Edwards 1 , Annette Shewan 1 , Melissa Brown 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

Mutations in the breast cancer susceptibility gene, BRCA1 confer an increased risk of developing breast cancer. Although the cellular and pathological consequences of BRCA1 disruption have been well documented, the early molecular consequences associated with these are not well characterized. Studies conducted on conditional Brca1 knockout mice, have revealed that they exhibit aberrant mammary gland morphogenesis and develop tumours with a similar histological and gene expression profile to human BRCA1 associated breast tumours. This makes the conditional Brca1 knockout mouse an excellent model to study molecular mechanisms of BRCA1 associated breast cancers. miRNAs play a role in the development and homeostatic regulation of the mammary gland and tumourigenesis of the mammary gland can occur if miRNAs are abnormally expressed. To investigate the role of miRNAs, a candidate approach was undertaken to shortlist miRNAs with known roles in breast cancer and mouse mammary gland development. The expression of the shortlisted miRNAs was then assessed in Brca1 deficient mice mammary tissue and mammary epithelial cell lines. A number of miRNAs demonstrated dysregulated expression in Brca1 depleted cells and tissues. Their effect on functional assays such as, epithelial polarity and differentiation has been determined and will be presented. Given that the uses of miRNAs are currently being trialed in the field of cancer, these studies may ultimately have therapeutic implications in the treatment of BRCA1 associated breast cancers.