Analysis of the molecular basis of individuality in RTK pathway expression in human ovarian tumours – identification of patient selection biomarkers for personalised cancer medicine

Growth factors (e.g. EGF, FGF, PDGF, VEGF) and associated receptor tyrosine kinases (RTKs) regulate key signal transduction pathways which are frequently dysregulated in cancer. RTK pathways are common targets in chemotherapy drug development, but optimal patient selection and drug efficacy is often limited by lack of target specificity.

EGF and TGFα Motogenic activities are mediated by the EGF receptor: Identification of the signalling pathways involved in oral cancer

Background and Aims: Cells need to migrate away from their microenvironment to enable the tumour to metastasise. The growth factors Epidermal Growth Factor (EGF) and Transforming Growth Factor α (TGFα) stimulate the migration of fibroblasts into 3D collagen gels. Experiments using a number of growth factors concluded that some stimulated Akt phosphorylation whilst others reduced the phosphorylation of this pathway, but all stimulated migration; suggesting that multiple pathways are important for cell motility.

The interaction between the Growth Factor VEGF and the Signal Transduction Molecule Akt in Oral Cancer

Project Background: The growth factor VEGF and a signal transduction pathway protein, Akt, may have an important role in oral tumours. Oral cancer patients from Dundee have been shown to have an increased expression of VEGF both in their tissue and in their serum. It has also been reported that Akt is activated in response to growth factors and this activation may be blocked by inhibitors.

The regulation of oncogenic signalling through the Ras/MAP kinase pathway by dual-specificity protein phosphatases

Signalling through the classical Ras/ERK MAP kinase pathway is implicated in the genesis and progression of human tumours carrying activating mutations is upstream pathway effectors such as receptor tyrosine kinases and the Ras family of cellular proto-oncogenes.

Spatial feedback controls during mitosis

Background: Two principle surveillance mechanisms have evolved to guard against errors during chromosome segregation. The mitotic checkpoint delays mitosis until each and every sister chromatid has achieved stable attachment to spindle microtubules (via a protein complex known as the kinetochore), and the microtubule error-correction pathway guides this attachment process by ensuring it remains free of errors. In spite of these safeguards, the majority of tumours still manage to continually missegregate their genome.

How do cells decide which pathway to use to repair DNA Breaks and what is the impact on cancer?

The DNA Damage Response (DDR) is a major component of a cells defence against disease. It serves to recognize and repair DNA damage, to regulate cell-cycle progression and where necessary, promote programmed cell death. One of the most potentially dangerous forms of DNA damage is a double stranded DNA break (DSB), which must be dealt with to maintain the structural and genetic integrity of a cell. Failure to do so results in generation of chromosomal aberrations such as chromosomal translocations that are potentially tumorigenic.

Control of the cell response to chemotherapy by modulating degradation of p53 protein isoforms

We demonstrated that the p53 tumour suppressor gene expresses at least twelve different p53 proteins due to alternative splicing, alternative initiation of translation and alternative promoter usage. We determined that p53 isoform proteins are expressed in normal human tissue in a tissue dependent manner. P53 isoforms are abnormally expressed in a wide range of cancer and are associated with breast cancer prognosis.


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