29P - Determining the role of the ETS factor ELF3 in normal and malignant prostate

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Basic Science
Prostate Cancer
Genitourinary Cancers
Presenter Leanne Archer
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors L.K. Archer, F.M. Frame, N.J. Maitland
  • Deaprtment Of Biology, Cancer Research Unit, University of York, YO10 5DD - York/GB

Abstract

Background

Aberrations in the ETS transcription factor family members are a common feature of multiple cancers including prostate cancer (PCa), such as the TMPRSS2:ERG fusion. ELF3, also known as ESE-1, is an epithelial-specific ETS transcription factor involved in regulating cell differentiation in various tissues, however, its role in the prostate is controversial. The aim of this study was to identify the function of ELF3 in normal prostate development and to explore its role in PCa.

Methods

Three model systems were used: prostate cell lines, primary prostate epithelial cells cultured from patient tissue and paraffin-embedded human tissue sections. The function of ELF3 was investigated using knockdown via siRNA transfection and overexpression via lentivirus transduction. Western blots, immunofluorescence and immunohistochemistry were used to measure protein localisation and levels of expression. Other assays measured cell viability, colony forming ability and migration.

Results

ELF3 expression was restricted to the basal layer of the normal prostate epithelium and was not expressed in stroma. Analysis of a prostate tissue microarray indicated that whilst ELF3 is expressed in benign prostate tissue, its expression is lost in low-grade prostate tumours and re-expressed in some more advanced tumours. ELF3 knockdown resulted in decreased migration, cell viability and did not induce stem cell characteristics, whilst promoting basal cell gene expression. ELF3 overexpression increased cell migration. ELF3 was induced in primary prostate epithelial cells following treatment with the clinically approved HDAC inhibitor Vorinostat, which can promote neuroendocrine differentiation.

Conclusions

ELF3 expression correlates with the normal prostate epithelial cell differentiation hierarchy, and may have a role in advanced PCa. Analysis of total gene expression following knockdown of ELF3 will give an indication of transcriptional networks that are regulated by ELF3. In addition, a lentivirus that expresses an ELF3 mutant, which alters its localisation, will be used to assess any cytoplasmic function of ELF3. This comprehensive and clinically relevant approach will allow complete elucidation of the role of ELF3 in prostate cell differentiation and PCa.

Clinical trial identification

N/A

Legal entity responsible for the study

Norman Maitland

Funding

Prostate Cancer UK (PCUK) registered charity

Disclosure

All authors have declared no conflicts of interest.