Details
- Close date
- Tuesday, 31 December 2024
- Academic background
- Health Sciences
- Host campus
- Dunedin
- Qualifications
- Honours, Master's
- Department
- Pathology (Dunedin)
- Supervisors
- Dr Sunali Mehta, Professor Antony Braithwaite
Overview
Δ133p53 is an isoform of tumour suppressor p53 that exhibits oncogenic properties.
We have shown that Δ133TP53 mRNA is elevated in a subset of prostate cancer (PCa) patients with shorter disease-free survival and is associated with increased inflammation. Furthermore, we discovered that Δ133p53 uses the IL-6-associated JAK/STAT3 and RhoA-ROCK signalling pathways to promote metastasis. We have also shown in PCa cells with wild-type p53 that Δ133p53 regulates the level of IL6ST (IL-6 signal transducer), which governs the activation of IL-6 mediated signalling pathways (JAK/STAT3, MAPKERK, and PI3K/AKT).
Our preliminary data suggest that, in the absence of functional JAK/STAT3 and MAPK/ERK pathways, Δ133p53 regulates the phosphorylation of AKT (pAKT). pAKT is known to regulate the expression of nuclear factor-κB (NFκB) and controls the transcriptional activity of its downstream target genes associated with inflammation.
The primary goal of the proposed project is to use gene editing to create the isogenic PCa cell lines stably expressing Δ133p53, characterise these cell lines using RT-qPCR and western blot technique and use RNA-sequencing and bioinformatics to identify genes involved in the IL6ST/AKT/NFκB signalling pathway and regulated by Δ133p53.
Useful information
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