Thesis
Examining the potential links between Inhibitory κB Kinases and Androgen receptors in castrate resistant prostate cancer
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2023
- Thesis identifier
- T16832
- Person Identifier (Local)
- 202180993
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Prostate cancer is one of the most common cancers which affect men. The cancer progresses in two stages: hormone naïve prostate cancer (HNPC) to castrate resistant prostate cancer (CRPC); a common theme surrounding prostate cancer is the increased expression of the Androgen receptor (AR). The NF-κB pathway, along with the IKK complex is involved in inflammatory responses including different cancers. One of these cancers is prostate cancer. The IKK complex is a protein complex made up of three subunits (IKKα, IKKβ and IKKγ). The complex is found inactive in the cytoplasm but becomes activated in both the canonical and non-canonical pathways. The purpose of this research was to determine a potential relationship between the IKK complex and AR status in cells representing CRPC; the aims being to understand this relationship between IKK levels and AR while also trying to determine whether the IKKs have any specific influence on the phosphorylation/status of the AR or not. Both an increase of the expression of cyclin D1 and p53 proteins were discovered, more so with p53 at the higher concentrations of the inhibitors SU1433 and SU1644. The stabilisation of Cyclin D1, in addition to increased p53 protein expression as a result of IKKα inhibition suggests that IKKα could be a potential clinical target. Immunoprecipitation experiments have shown no binding between IKKα and AR but further investigation is needed. Finally, a potential link between IKKα and the androgen receptor was discovered; shown by a reduction in AR expression after LNCaP AI cells were exposed to both inhibitors. Whether this relationship is direct or indirect through mRNA destabilisation, direct degradation, or the inhibition of AR gene expression still remains to be seen. Using more AR positive cell lines, in addition to extending experiments to analyse other cancer related proteins, would help provide a clearer picture of the relationship between the IKK complex, AR and other cancer related proteins.
- Advisor / supervisor
- Paul, Andrew
- Resource Type
- DOI
- Embargo Note
Relations
Items
| Thumbnail | Title | Date Uploaded | Visibility | Actions |
|---|---|---|---|---|
|
|
File | 2024-02-20 | University of Strathclyde |