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Title: Regulation of Fos related antigen-1 (Fra-1) accumulation in human bladder cancer
Authors: Stanford, Richard Frederick John
Supervisors: Mellon, John
Tulchinsky, Eugene
Award date: 1-Nov-2012
Presented at: University of Leicester
Abstract: 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.
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Description: Due to copyright restrictions the published articles have been removed from Appendix 2 (pp. 213-223) of the electronic version of this thesis. The unabridged version can be consulted, on request, at the University of Leicester’s David Wilson Library.
Appears in Collections:Theses, Dept. of Cancer Studies & Molecular Medicine
Leicester Theses

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