Polycomb proteins and breast cancer

Abstract

In the Western world, breast cancer is the most frequent malignancy in women and still the leading cause of cancer related deaths, therefore, a better understanding of the disease is needed. Adequate therapeutic targets for all breast cancer types have not been identified yet, and patients with the same type of cancer have often different outcomes. Polycomb proteins are emerging as important factors involved in breast cancer formation. Polycomb proteins play a crucial role in embryogenesis, early development, stem cell renewal and establishing and maintaining cell identity. Their alteration leads to mis-regulation of several important cellular factors including tumour suppressors, DNA repair factors, cell cycle regulation factors and cell-cell interaction factors. In this thesis the importance of several polycomb proteins in breast cancer has been investigated. The effect of EZH2 knockdown has been tested in breast cancer cell lines expressing different level of the protein and with different features. The results obtained are in line with other studies and suggest that the effect of EZH2 down-regulation in breast cancer cells is dependent on cellular context. In vitro experiments, using both established breast cell lines and primary epithelial cells have been used for investigating the importance of CBX8 in breast cancer. The results obtained showed that the polycomb proteins CBX8 does not play a central role in malignant transformation of the mammary epithelial cells tested.