Stem cells and the role of ETS transcription factors in the differentiation hierarchy of normal and malignant prostate epithelium.
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.
['Archer|Leanne K|LK|', 'Frame|Fiona M|FM|', 'Maitland|Norman J|NJ|']
D000818:Animals D017209:Apoptosis D002454:Cell Differentiation D004847:Epithelial Cells D004848:Epithelium 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 D010641:Phenotype D011467:Prostate D011471:Prostatic Neoplasms D050783:Proto-Oncogene Proteins c-ets D016896:Treatment Outcome
Prostate cancer Treatment resistance Cancer stem cells ETS factors