Role of Growth factor receptor-bound protein 7 (Grb7) in mammary tumour progression

Gene amplification and elevated expression of ErbB2 receptor tyrosine kinase has been implicated in the development and progression of human breast cancer, and correlates to poor clinical outcomes. Transgenic mouse models provide a good tool to study ErbB2 mediated mammary tumourigenesis. In both human ErbB2 positive mammary tumour and ErbB2 knock-in mouse model derived mammary tumours, Grb7 is found to be co-amplified and co-expressed with ErbB2. Here we demonstrated ectopic expression of Grb7 in MDCK cells correlates to the loss of epithelial cell polarity, and this was also found true in primary mammary epithelial cells derived from transgenic mice overexpressing Grb7. Elevated expression of Grb7 in mouse mammary gland during developing stage can lead to incomplete mammary ductal outgrowth accompanied by mammary ducts with multiple epithelial layers and myoepithelial missing. NDL transgenic overexpressing Grb7 had longer tumour latency, and it was found that NDL tumours selectively down-regulated the induced-expression of Grb7.