title: Telomerase Activity and Telomere Length in Human Benign Prostatic Hyperplasia Stem-like Cells and Their Progeny Implies the Existence of Distinct Basal and Luminal Cell Lineages.
abstract: Benign prostatic hyperplasia (BPH) treatments have changed little over many years and do not directly address the underlying cause. Because BPH is characterised by uncontrolled cell growth, the chromosomal telomeres should be eroded in the reported absence or low levels of telomerase activity, but this is not observed. We investigated the telomere biology of cell subpopulations from BPH patients undergoing transurethral resection of prostate (TURP). Measurement of TERC, TERT, and telomerase activity revealed that only the epithelial stem-like and progenitor fractions expressed high levels of telomerase activity (p<0.01) and individual enzyme components (p<0.01). Telomerase activity and TERT expression were not detected in stromal cells. Telomere length measurements reflected this activity, although the average telomere length of (telomerase-negative) luminal cells was equivalent to that of telomerase-expressing stem/progenitor cells. Immunohistochemical analysis of patient-derived BPH arrays identified distinct areas of luminal hyperproliferation, basal hyperproliferation, and basal-luminal hyperproliferation, suggesting that basal and luminal cells can proliferate independently of each other. We propose a separate lineage for the luminal and basal cell components in BPH.
  
  
  RESULTS
  We unexpectedly found an enzyme called telomerase in the cells that maintain benign prostatic hyperplasia (BPH), suggesting that telomerase inhibitors could be used to alleviate BPH symptoms.
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK.
authors.forename: Jayant K
authors.initials: JK
authors.lastname: Rane
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Greener
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Frame
authors.affiliation: Hull York Medical School, University of Hull, Hull, East Yorkshire, UK; Department of Urology, Castle Hill Hospital, Cottingham, East Yorkshire, UK.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Mann
authors.affiliation: Hull York Medical School, University of Hull, Hull, East Yorkshire, UK; Department of Urology, Castle Hill Hospital, Cottingham, East Yorkshire, UK.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Simms
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Collins
authors.affiliation: Centre for Molecular Oncology and Imaging, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK; Hull York Medical School, University of Hull, Hull, East Yorkshire, UK. Electronic address: n.j.maitland@york.ac.uk.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Maitland
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D010641:Phenotype; D011467:Prostate / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D012313:RNA / Q000378:metabolism; D013234:Stem Cells / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D020728:Transurethral Resection of Prostate
chemical_list: D015415:Biomarkers; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase
keywords: Benign prostatic hyperplasia; Stem cells; Telomerase