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

• Published in: European urology 2016-04, Vol.69 (4), p.551-554
• Main Authors: Rane, Jayant K, Greener, Sarah, Frame, Fiona M, Mann, Vincent M, Simms, Matthew S, Collins, Anne T, Berney, Daniel M, Maitland, Norman J
• Format: Article
• Language: English
• Subjects: Benign prostatic hyperplasia; Biomarkers - metabolism; Cell Lineage; Cell Proliferation; Humans; Male; Phenotype; Prostate - enzymology; Prostate - pathology; Prostate - surgery; Prostatic Hyperplasia - enzymology; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - pathology; Prostatic Hyperplasia - surgery; RNA - metabolism; Stem cells; Stem Cells - enzymology; Stem Cells - pathology; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomere Homeostasis; Transurethral Resection of Prostate; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2015.09.039

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. Patient summary 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.