Bladder cancer is one of the commoner malignancies in humans and current treatments for invasive disease typically give a five year survival rate of around fifty percent. Current chemotherapeutic agents increase survival by a small amount; clearly there is the need for improved treatments and for this, novel targets need to be identified. One putative target is the Fos family member Fos-related antigen-1 (Fra-1), which form part of the AP-1 transcription factor complex. Fra-1 is elevated in numerous human malignancies and regulates the transcription of genes involved in many aspects of the malignant process, such as migration and invasion. Regulatory control of Fra-1 has been incompletely studied to date; it is known that MAP Kinase dependent signalling can influence Fra-1 accumulation but other aspects of control are only now being elucidated. This thesis demonstrates that Fra-1 is present in the majority of bladder cancers, that it is regulated by the structure of the C-terminus and MAP Kinase dependent phosphorylation of the amino acids Ser[superscript 252] and Ser[superscript 265], and undergoes proteasomal degradation. This highlights the potential role of Fra-1 as a novel therapeutic target and provides more information on the regulation of Fra-1 which may be targeted with novel agents.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:593653 |
| Date | January 2012 |
| Creators | Stanford, Richard Frederick John |
| Contributors | Mellon, John; Tulchinsky, Eugene |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/28237 |
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