The Expression of the Prion Protein (PrP) in Common Cancers and its Role in the Metastasis of Breast Cancer and Development of Chemotherapeutic Drug Resistance in Colon and Breast Cancer

Abstract

Renowned for its role in a number of human and other animal neurodegenerative diseases known as prion diseases, the cellular prion protein (PrPC) has recently been implicated in the development, progression and drug-resistance of numerous cancers. These cancers include gastric, breast, colon and pancreatic. While there has been considerable research into the role that PrPC plays in the development and progression of cancer, there is still much to be elucidated, including (but not limited to) the mechanisms of action of PrPC in drug-resistance and metastasis. The work presented in this thesis aimed to further knowledge of the role that PrPC plays in cancer development, metastasis, and drug-resistance. Firstly, we examined the expression of PrPC at the gene and protein level in a range of cell lines derived from common cancers including colon, prostate, skin and breast cancer cell lines, comparing PrPC expression levels in these cancer cell lines with the PrPC expression level in a control non-cancerous cell line. Secondly, we began to explore the role of PrPC in chemotherapeutic drug-resistance in colon cancer and identified a potential mechanism by which PrPC confers cisplatin-resistance. Thirdly, we examined the expression and influence of PrPC on metastasis of breast cancer and addressed the key question of whether PrPC in conditioned media from highly metastatic breast cancer cells can transfer a metastatic phenotype to previously non-metastatic breast cancer cells. Lastly, we examined the influence of PrPC on the sensitivity of breast cancer cells to doxorubicin treatment.