ArticleThe Prostate2010
Prostate-specific antigen (PSA) is activated by KLK2 in prostate cancer ex vivo models and in prostate-targeted PSA/KLK2 double transgenic mice.
Article in The Prostate, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- The molecular heterogeneity and clinical impact of genomic driver alterations in prostate cancer.Nature communications · 2026Article
- Inhibition of Growth and Induction of Apoptosis of Human Prostate Cancer Cells by Enzymatic Blockage of Kallikreins.Prostate cancer · 2026Article
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Human Kallikrein 2: A Novel Lineage-Specific Surface Target in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The roles of proteases in prostate cancer.IUBMB life · 2023Review
- GeneFriends: gene co-expression databases and tools for humans and model organisms.Nucleic acids research · 2023Article
- A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion.Journal of the American Chemical Society · 2022Article
- Article
- The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment.International journal of molecular sciences · 2022Review
- KLK3 in the Regulation of Angiogenesis-Tumorigenic or Not?International journal of molecular sciences · 2021Review
- A Suite of Activity-Based Probes To Dissect the KLK Activome in Drug-Resistant Prostate Cancer.Journal of the American Chemical Society · 2021Article
- BRG1 knockdown inhibits proliferation through multiple cellular pathways in prostate cancer.Clinical epigenetics · 2021Article
- Putting the Pieces Together: Completing the Mechanism of Action Jigsaw for Sipuleucel-T.Journal of the National Cancer Institute · 2020Review
- The age-specific reference intervals for tPSA, fPSA, and %fPSA in healthy Han ethnic male.Journal of clinical laboratory analysis · 2017Article
- Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment.Journal of the National Cancer Institute · 2017Review
- A Single Glycan at the 99-Loop of Human Kallikrein-related Peptidase 2 Regulates Activation and Enzymatic Activity.The Journal of biological chemistry · 2016Article
- KLK-targeted Therapies for Prostate Cancer.EJIFCC · 2014Article
- Human kallikrein 2 (KLK2) promotes prostate cancer cell growth via function as a modulator to promote the ARA70-enhanced androgen receptor transactivation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: the ABRF glycoprotein research multi-institutional study 2012.Molecular & cellular proteomics : MCP · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProstate-specific antigen (PSA) is a serine protease secreted as a zymogen. Previously, cell-free biochemical studies have identified various kallikreins (KLK) as candidate activating proteases. In this study, KLK2-mediated activation of PSA in cell-based in vitro, xenograft, and transgenic models was evaluated.
methodsDu145-derived PSA- or KLK2-expressing clones were coincubated in vitro and in vivo to evaluate KLK2-induced PSA activity. While mice possess orthologs of KLK4-15, they do not have functional orthologs of PSA or KLK2. Therefore, transgenic animals expressing PSA or both PSA and KLK2 were generated to assess orthotopic PSA activation.
resultsPSA is activated by KLK2 when the cells are physically in contact, and through co-conditioned media. In vivo, the free (inactive PSA) to total (active + inactive PSA) ratio in the blood is decreased when PSA and KLK2-expressing cells are co-inoculated subcutaneously, suggesting increased active PSA. Additionally, double-transgenic mice expressing both genes in the prostate produce more active PSA compared to single transgenic animals. A longitudinal evaluation over a 2-year period demonstrated no morphologic changes (i.e., no PIN or prostate cancer) due to PSA or PSA/KLK2 double transgene expression relative to non-transgenic mice.
conclusionsThese data demonstrate, with biologically relevant models, that KLK2 is the protease responsible for activating PSA. While PSA is involved in the processing and release of a number of important growth factors, our results suggest that active PSA is not sufficient to induce the development of prostate cancer or prostate cancer precursors in aging PSA transgenic mice.
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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.