Packer, John R and Maitland, Norman J orcid.org/0000-0003-1607-9035 (2016) The molecular and cellular origin of human prostate cancer. Biochimica et biophysica acta. pp. 1238-1260. ISSN 0006-3002
Abstract
Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Biology (York) > Yorkshire Cancer Research Unit (York) |
Depositing User: | Pure (York) |
Date Deposited: | 29 Mar 2016 12:57 |
Last Modified: | 21 Jan 2025 17:20 |
Published Version: | https://doi.org/10.1016/j.bbamcr.2016.02.016 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1016/j.bbamcr.2016.02.016 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97255 |
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