Tyrosine kinase signalling in breast cancer - Tyrosine kinase-mediated signal transduction in transgenic mouse models of human breast cancer

The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal transduction pathways. Aberrant ex pression of specific receptor tyrosine kinases (RTKs) has been implicated i n the genesis of a significant proportion of sporadic human breast cancers. Indeed, mammary epithelial expression of activated RTKs such as ErbB2/neu in transgenic mice has resulted in the efficient induction of metastatic ma mmary tumours. Although it is clear from these studies that activation thes e growth factor receptor signalling cascades are directly involved in mamma ry tumour progression, the precise interaction of each of these signalling pathways in mammary tumourigenesis and metastasis remains to be elucidated. The present review focuses on the role of several specific signalling path ways that have been implicated as important components in RTK-mediated sign al transduction. In particular, it focuses on two well characterized transg enic breast cancer models that carry the polyomavirus middle T (PyV mT) and neu oncogenes.