This project will examine if the smaller forms of p53 can promote migration and invasion in breast cancer cells.
In order to do this, we will:
1) Examine the affect of high or low levels of p53 isoforms on growth, invasion and migration in breast cancer cell line models (three-dimensional, to replicate the structure of the breast).
2) Examine what target genes the isoforms affect (in cell lines and in clinical samples) to alter these processes of migration and invasion that ultimately lead to poorer outcomes in breast cancer patients.
The incidence of breast cancer continues to rise and there are still few effective preventative treatments for metastatic disease (or secondary cancers). The p53 pathway is one of the most important pathways regulating breast proliferation. We will investigate a novel mechanism by which this pathway becomes disrupted and this will have significant implications for breast cancer progression and treatment response. At the completion of this study, we will know if high expression of the p53 isoform, Δ40p53, is associated with breast cancer development and aggressiveness; and whether it can alter the migratory and invasive capacity of breast cancer cells- hallmarks of metastastic progression, which is at present, untreatable. In the short term, this information could be used to more accurately determine breast cancer prognosis. A long term outcome is that new treatments could be developed to inhibit Δ40p53, thereby reactivating p53, increasing the effectiveness of current therapies and lessening the impact of breast cancer in the community.