C59
Investigating the role of Fibroblast growth factor 2 in breast cancer
Anja Mueller, Louise J. Jones, Richard Grose
Centre for Tumour Biology, Institute of Cancer, Barts and The London, Queen Mary University of London, London, UK
Two recent genome-wide association studies have identified FGFR2 unequivocally as a clear candidate gene, contributing to inherited risk of developing breast cancer, the implication being that the variant allele results in over-expression of the tyrosine kinase FGFR2. Amplification of FGFR2 has been identified in up to 10% of breast cancers, supporting a role for over-expression of this receptor in this disease. However, little is understood about how, and at what stage, FGFR2 may contribute to breast cancer development or progression and there are few experimental studies that have addressed this issue.
We are investigating the functional role of FGFR2 in breast cancer by conducting a series of cell-based studies complemented by extensive analysis of human breast cancer samples. This will provide greater understanding of the role of FGFR2 activity in modulating normal and malignant breast epithelial cell function.
We are screening TMAs of human breast tumour samples and normal breast for FGFR2 expression, localisation and splicing using immunohistochemistry and in-situ hybridisation studies. Alongside this, we have developed two organotypic 3D culture approaches where FGF signalling can be modulated within a simplified in vivo model of breast cancer. Using such models, we have introduced inducible FGFR2 expression vectors and treated with small molecule inhibitors. These ongoing studies will allow us to elucidate the functional significance of FGF signalling in breast cancer pathology.
