ArticleOncogene2010
Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Polyphenols in food and food wastes: Extraction, isolation, and health applications.Food chemistry. Molecular sciences · 2026Review
- Alox8 knockout exacerbates imiquimod-induced psoriasis-like inflammation.Cell death & disease · 2026Article
- Genetic Liability to COPD and Periodontitis Risk: Integrative Genetic and Single-Cell Evidence Implicating Macrophage Reprogramming.International journal of chronic obstructive pulmonary disease · 2026Article
- Developing the risk prediction model (ProlncSig) from lipoxygenase pathway-related lncRNAs for prognosis prediction in breast cancer.RNA biology · 2025Article
- Arachidonic acid in aging: New roles for old players.Journal of advanced research · 2025Review
- Murine Alox8 versus the human ALOX15B ortholog: differences and similarities.Pflugers Archiv : European journal of physiology · 2024Review
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024Review
- Air Pollution Drives Macrophage Senescence through a Phagolysosome-15-Lipoxygenase Pathway.ImmunoHorizons · 2024Article
- Air pollution drives macrophage senescence through a phagolysosome-15-lipoxygenase pathway.bioRxiv : the preprint server for biology · 2024Article
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
- Male Knock-in Mice Expressing an Arachidonic Acid Lipoxygenase 15B (Alox15B) with Humanized Reaction Specificity Are Prematurely Growth Arrested When Aging.Biomedicines · 2022Article
- Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology.Frontiers in pharmacology · 2022Review
- miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities.Oncogenesis · 2021Article
- Evidence for context-dependent functions of KDM5B in prostate development and prostate cancer.Oncotarget · 2020Article
- Trop2: Jack of All Trades, Master of None.Cancers · 2020Review
- Ring/U-Box Protein AtUSR1 Functions in Promoting Leaf Senescence Through JA Signaling Pathway in Arabidopsis.Frontiers in plant science · 2020Article
- LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.Nature communications · 2019Article
- Stylosin and some of its synthetic derivatives induce apoptosis in prostate cancer cells as 15-lipoxygenase enzyme inhibitors.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Regulation and Functions of 15-Lipoxygenases in Human Macrophages.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
15-Lipoxygenase 2 (15-LOX2), a lipid-peroxidizing enzyme, is mainly expressed in the luminal compartment of the normal human prostate, and is often decreased or lost in prostate cancer. Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we generated prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, transgenic expression of 15-LOX2 or 15-LOX2sv-b, a splice variant that lacks arachidonic acid-metabolizing activity, resulted in age-dependent prostatic hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in luminal and Ki-67(+) cells; however, 15-LOX2-transgenic prostates also showed a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2, but not 15-LOX2sv-b, transgenic prostate showed upregulation of several well-known stem or progenitor cell molecules including Sca-1, Trop2, p63, Nkx3.1 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to prostatic intraprostate neoplasia or carcinoma and, mechanistically, prostate lobes (especially those of 15-LOX2 mice) showed a dramatic increase in senescent cells as revealed by increased SA-betagal, p27(Kip1) and heterochromatin protein 1gamma staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia and also induces cell senescence, which may, in turn, function as a barrier to tumor development.
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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.