title: Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium.
abstract: Prostate cancer is the most common cancer of men in the UK and accounts for a quarter of all new cases. Although treatment of localised cancer can be successful, there is no cure for patients presenting with invasive prostate cancer and there are less treatment options. They are generally treated with androgen-ablation therapies but eventually the tumours become hormone resistant and patients develop castration-resistant prostate cancer (CRPC) for which there are no further successful or curative treatments. This highlights the need for new treatment strategies. In order to prevent prostate cancer recurrence and treatment resistance, all the cell populations in a heterogeneous prostate tumour must be targeted, including the rare cancer stem cell (CSC) population. The ETS transcription factor family members are now recognised as a common feature in multiple cancers including prostate cancer; with aberrant expression, loss of tumour suppressor function, inactivating mutations and the formation of fusion genes observed. Most notably, the TMPRSS2-ERG gene fusion is present in approximately 50% of prostate cancers and in prostate CSCs. However, the role of other ETS transcription factors in prostate cancer is less well understood. This review will describe the prostate epithelial cell hierarchy and discuss the evidence behind prostate CSCs and their inherent resistance to conventional cancer therapies. The known and proposed roles of the ETS family of transcription factors in prostate epithelial cell differentiation and regulation of the CSC phenotype will be discussed, as well as how they might be targeted for therapy.
authors.affiliation: Cancer Research Unit, Department of Biology, University of York, York, YO10 5DD, United Kingdom.
authors.forename: Leanne K
authors.initials: LK
authors.lastname: Archer
authors.affiliation: Cancer Research Unit, Department of Biology, University of York, York, YO10 5DD, United Kingdom.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Frame
authors.affiliation: Cancer Research Unit, Department of Biology, University of York, York, YO10 5DD, United Kingdom. Electronic address: n.j.maitland@york.ac.uk.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Maitland
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000502:physiology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010641:Phenotype; D011467:Prostate / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D050783:Proto-Oncogene Proteins c-ets
keywords: Cancer stem cells; ETS factors; Prostate cancer; Treatment resistance