ArticleJournal of hematology & oncology2020
ETV4 promotes late development of prostatic intraepithelial neoplasia and cell proliferation through direct and p53-mediated downregulation of p21.
Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Relationship between expression of OGFR, P16, P21 and clinicopathological features of colorectal cancer patients.Journal, genetic engineering & biotechnology · 2026Article
- Fingered Citron Volatile Oil: Extraction Methods, Chemical Composition, Biological Activity, and Product Development.Current issues in molecular biology · 2026Review
- Aumolertinib combined with targetingJournal of thoracic disease · 2026Article
- SLPI in Prostate Cancer.Cancers · 2026Review
- Emerging role of ETV4 in colorectal cancer: from molecular mechanisms to clinical implications.Frontiers in oncology · 2026Review
- Oncotransformation in Bhas 42 Cell Transformation Assay by Typical Non-Genotoxic Carcinogens, PFOA and PFOS, and Time-Course Transcriptome Analysis.Biomolecules · 2025Article
- Article
- Comprehensive analysis of the functional and immunological significance of ETV4 in pan-cancer and its validation in digestive tumors.Frontiers in immunology · 2025Article
- Biological effect of ETV4 and the underlying mechanism of its regulatory effect on epithelial‑mesenchymal transition in intrahepatic cholangiocarcinoma cells.Oncology letters · 2024Article
- Prenatal nicotine exposure leads to epigenetic alterations in peripheral nervous system signaling genes in the testis of the rat.Epigenetics & chromatin · 2024Article
- Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-α signaling.Cancer communications (London, England) · 2023Article
- ETV4 facilitates proliferation, migration, and invasion of liver cancer by mediating TGF-β signal transduction through activation of B3GNT3.Genes & genomics · 2023Article
- Article
- Identification and characterization of novel ETV4 splice variants in prostate cancer.Scientific reports · 2023Article
- Knockdown of ETV4 promotes autophagy-dependent apoptosis in GBM cells by reducing the transcriptional activation of EMP1.Oncology letters · 2022Article
- ETV4 promotes breast cancer cell stemness by activating glycolysis and CXCR4-mediated sonic Hedgehog signaling.Cell death discovery · 2021Article
- Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies.Molecular oncology · 2021Article
- Single-Cell Gene Network Analysis and Transcriptional Landscape of MYCN-Amplified Neuroblastoma Cell Lines.Biomolecules · 2021Article
- Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer.American journal of cancer research · 2020Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model.
methodsWe have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays.
resultsETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice, cdkn1a and its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in the CDKN1A promoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controls CDKN1A expression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice.
conclusionsETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation of CDKN1A and its p21 protein product: this in turn is mediated through direct binding of ETV4 to the CDKN1A promoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.
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