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Does the D133p53 isoform promote cancer invasion and metastasis?

45 months
Approved budget:
Professor Antony Braithwaite
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
This proposal addresses the hypothesis that human 133p53 protein variant promotes tumour invasion and metastasis (tumour spread) via inflammation, and as such is a key contributor to cancer mortality. We will address this in part using a genetically modified mouse we generated that makes a protein ( 122p53) similar to human 133p53. This is the only available mouse model of 133p53. We will examine 122p53 mice in detail for evidence of metastasis and angiogenesis (development of a tumour blood supply). In parallel, based on leads from analysis of 122p53 mice and gene analysis of human tumours, we will investigate whether 122p53 promotes invasion in cell culture and regulates the activity of the pro-inflammatory gene, IL-6, known to promote metastasis. We will analyse human cancers to investigate a relationship between 133p53 levels, inflammatory gene activities and tumour metastasis. As patients die of metastasis, understanding this process provides the best option for intervention.