We will present data showing that Notch signalling is activated in a wide range of breast cancer cell lines and in a panel of 20 human breast carcinomas of different pathological grade and prognosis. In addition, we will demonstrate that sustained signalling is required to maintain the transformed phenotype of breast cancer cell lines, as its inhibition by expressing Numb, a natural inhibitor of the pathway, causes both MCF7 and MDA-MB-231 cells to adopt a normal phenotype. Our data with the normal breast epithelial cell line MCF 10A indicate that Notch signalling contributes to the transformed phenotype by inhibiting apoptosis. Activation of Notch signalling in these cells by overexpressing the Notch1 intracellular domain prevents apoptosis in response to growth factor withdrawal, removal from the extracellular matrix and DNA damage. Finally, we will provide evidence that the apoptosis resistance seen in Notch transformed MCF 10A cells is through the activation of the Akt survival pathway.