ArticleThe Journal of clinical investigation2009
Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Genetic variants within endothelial nitric oxide synthase gene and prostate cancer: a meta-analysis.Clinical and translational science · 2015Pooled it
- The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review.Journal of cancer research and clinical oncology · 2013Pooled it
- Corynoline enhances sorafenib sensitivity in hepatocellular carcinoma via NOS3-mediated ROS production.Chinese medicine · 2025Article
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Article
- Prognostic Impact of H19/Cell Adhesion Molecules Circuitry on Prostate Cancer Biopsy.Biomedicines · 2024Article
- The role of HIF in angiogenesis, lymphangiogenesis, and tumor microenvironment in urological cancers.Molecular biology reports · 2023Review
- Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.Frontiers in endocrinology · 2023Review
- The Impact of Lifestyle on Prostate Cancer: A Road to the Discovery of New Biomarkers.Journal of clinical medicine · 2022Review
- Pillars and Gaps of S-Nitrosylation-Dependent Epigenetic Regulation in Physiology and Cancer.Life (Basel, Switzerland) · 2021Review
- Hypoxia- and dexamethasone-dependent HIF1α-glucocorticoid receptor interaction leads to degradation of glucocorticoid receptor in pituitary adenomas.American journal of translational research · 2021Article
- Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity.PloS one · 2020Article
- Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies.Journal of experimental & clinical cancer research : CR · 2019Article
- The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells.Scientific reports · 2019Article
- Review
- H19-Dependent Transcriptional Regulation of β3 and β4 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer.International journal of molecular sciences · 2019Article
- Altered Nup153 Expression Impairs the Function of Cultured Hippocampal Neural Stem Cells Isolated from a Mouse Model of Alzheimer's Disease.Molecular neurobiology · 2019Article
- Intratumoral Sterol-27-Hydroxylase (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Article
- Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism.Antioxidants & redox signaling · 2019Review
- Molecular docking of genistein on estrogen receptors, promoter region of BCLX, caspase-3, Ki-67, cyclin D1, and telomere activity.Journal of Taibah University Medical Sciences · 2019Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 9 institutions in 2 countries.
Funding
Abstract
The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor beta (ERbeta). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERbeta/eNOS, ERbeta/HIF-1alpha, or ERbeta/HIF-2alpha combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERbeta and nuclear eNOS plus HIF-2alpha being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERbeta, and HIF-2alpha expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.