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The role of the ETS factor ELF3 in the normal and malignant prostate
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The role of the ETS factor ELF3 in the normal and malignant prostate
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Dissertation
The role of the ETS factor ELF3 in the normal and malignant prostate
2018
Overview
The ETS transcription factor family members are involved in multiple cancers, including prostate cancer. Whilst extensive literature exists on the highly prevalent TMPRSS2-ERG gene fusion, the role of other ETS factors in prostate cancer is less well understood. ELF3 has been ascribed both oncogenic and tumour suppressive roles in prostate cancer and has been highlighted as a regulator of epithelial cell differentiation in other tissues. The overarching aim of this project was to elucidate the role of ELF3 in the context of both normal prostate development and prostate cancer. This study details an extensive expression profile of ELF3 in prostate epithelial cell lines, primary prostate cell subpopulations and prostate tissue. ELF3 expression was restricted to the basal compartment of epithelial glands, specifically to the committed basal cell subpopulation of the basal epithelial hierarchy. Appropriate cell models were used to investigate the role of ELF3 in the prostate. By silencing ELF3 in BPH-1 and PC3 cells, ELF3 was established as a regulator of the cell cycle. This manifested as a decrease in colony forming ability, migration and cell viability caused by G2 cell cycle arrest. Furthermore, manipulating ELF3 expression altered the differentiation status of cell lines and primary cells, highlighting that a balance of ELF3 expression is required to maintain proper differentiation of the epithelial hierarchy. Finally, a possible link of ELF3 to more advanced prostate tumours using tissue microarray analysis, a potential association with neuroendocrine differentiation and putative survival advantage of ELF3 expression in cancer vs normal cells, was identified. These results suggest that ELF3 acts as an oncogene in the prostate cancer setting. However, its importance in normal prostate epithelial cell growth and differentiation has also been demonstrated. Work should now focus on identifying appropriate downstream effectors that could be targeted to exploit these properties for prostate cancer treatment.
Publisher
ProQuest Dissertations & Theses
Subject
