Award details

The role and regulation of Fra-1 and JunB in Ras transformation

Reference	BBS/E/B/0000H413
Principal Investigator / Supervisor	Dr Simon Cook
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	96,521
Status	Completed
Type	Institute Project
Start date	01/10/1998
End date	30/09/2003
Duration	60 months

Abstract

Cancer cells exhibit aberrant gene expression and it is the expression of some of these genes which is responsible for the cancerous properties of the cell. A family of genes called AP-1 are frequently found at high levels in many cancer cells. Furthermore, if AP-1 genes are artificially introduced into normal cells they become cancerous. This project aims to understand what signals in the cancer cell lead to elevated expression of AP-1 genes. The purpose of this proposal is to elucidate the role of Fra-1, Fra-2, c-Jun and JunB in regulating Ras-stimulated cell cycle progression and transformation with particular emphasis on Fra-1 and JunB. The early work will be analytical, continuing on from my preliminary results. Using EMSA and co-immunoprecipitation analysis the qualitiative make-up of AP-1 dimers assembled in response to growth factors, Raf-1:ER and RasV12 will be analysed in normal immortalised fibroblasts and a series of cell lines representing different stages of epidermal tumour progression. The second phase of work will be to validate the role of these dimer pairs in the proliferative and invasive aspects of Ras transformation in immortalised fibroblasts and their ability to enhance the pre-malignant phenotype of early stage epidermal tumour cell lines. In particular, the role of Fra-1 and JunB in Ras transformation will be assessed in knockout fibroblasts and by constructing candidate dominant inhibitory mutants, the effects of which will be analysed in fibroblasts and tumour cell lines. Finally, the study will address the possible role of phosphorylation in regulating the properties and functions of Fra-1 and JunB. These studies should allow an assessment of the role of Fra-1 and JunB in Ras transformation, in terms of necessity and sufficiency, thereby validating them as possible targets for translational research.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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