ArticleThe Journal of biological chemistry2008
Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Human intermediate prostate cancer stem cells contribute to the initiation and development of prostate adenocarcinoma.Stem cell research & therapy · 2024Article
- Derivation of human primary prostate epithelial cell lines by differentially targeting the CDKN2A locus along with expression of hTERT.Scientific reports · 2024Article
- Derivation of human primary prostate epithelial cell lines by differentially targeting theResearch square · 2024Article
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
- Upregulated PPARG2 facilitates interaction with demethylated AKAP12 gene promoter and suppresses proliferation in prostate cancer.Cell death & disease · 2021Article
- Immortalization of human primary prostate epithelial cells via CRISPR inactivation of the CDKN2A locus and expression of telomerase.Prostate cancer and prostatic diseases · 2021Article
- Tumor Dormancy and Slow-Cycling Cancer Cells.Advances in experimental medicine and biology · 2019Review
- Low p16The Prostate · 2017Article
- Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors that Can Function as a Cell of Origin for Prostate Cancer.Stem cells translational medicine · 2017Article
- Article
- Advances in prostate cancer research models: From transgenic mice to tumor xenografting models.Asian journal of urology · 2016Review
- Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.Nature communications · 2016Article
- Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells.Oncotarget · 2015Article
- Tumor-suppressive functions of 15-Lipoxygenase-2 and RB1CC1 in prostate cancer.Cell cycle (Georgetown, Tex.) · 2014Article
- Article
- Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells.World journal of gastroenterology · 2012Article
- The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration.Cell stem cell · 2012Article
- Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor.Breast cancer research : BCR · 2011Article
- The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.Nature medicine · 2011Article
- Drug-tolerant cancer cells show reduced tumor-initiating capacity: depletion of CD44 cells and evidence for epigenetic mechanisms.PloS one · 2011Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo, but the underlying molecular mechanisms remain obscure. Here we show that the senescence of primary NHP cells, which are immunophenotyped as intermediate basal-like cells expressing progenitor cell markers CD44, alpha2beta1, p63, hTERT, and CK5/CK18, involves loss of telomerase expression, up-regulation of p16, and activation of p53. Using genetically defined manipulations of these three signaling pathways, we show that p16 is the primary determinant of the NHP cell proliferative capacity and that hTERT is required for unlimited proliferative life span. Hence, suppression of p16 significantly extends NHP cell life span, but both p16 inhibition and hTERT are required to immortalize NHP cells. Importantly, immortalized NHP cells retain expression of most progenitor markers, demonstrate gene expression profiles characteristic of proliferating progenitor cells, and possess multilineage differentiation potential generating functional prostatic glands. Our studies shed important light on the molecular mechanisms regulating the proliferative life span of NHP progenitor cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.