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The role of p53 isoforms for increased cancer susceptibility

36 months
Approved budget:
Dr Tania Slatter
Health issue:
Cancer (oncology)
Proposal type:
Emerging Researcher First Grant
Lay summary
We know p53 is a powerful suppressor of cancer. Defects in this protein, caused by p53 gene mutations, are a well-known contributor to cancer development. Naturally occurring variants of p53 (isoforms) have been discovered, and one of these, 133p53, has increased expression in human tumours. We have developed a model to study this variant. Our preliminary data suggests 133p53 promotes cancer and exposed two-candidate means: by increasing cellular proliferation (growth) and by increasing inflammation (the bodies reaction to infection and irritation). Mysteriously, many cancers develop in a background of proliferation and inflammation. We aim to characterise the pro-proliferative and inflammatory function of 133p53 in greater detail; identify the specific pathways involved; and show that these pathways accompany 133p53 expression in human cancers and in pre-cancerous lesions (before a cancer has developed). These advances will provide important diagnostic and prognostic (prediction of patient out-come) aids, and in the longer-term may assist drug treatment development.