2013StanfordRPhD.pdf (22.07 MB)
Regulation of Fos related antigen-1 (Fra-1) accumulation in human bladder cancer
thesis
posted on 2013-10-01, 09:34 authored by Richard Frederick John StanfordBladder 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.
History
Supervisor(s)
Mellon, John; Tulchinsky, EugeneDate of award
2012-11-01Awarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- PhD