{"title":"Targeting TGCT","authors":"Louise Lloyd","doi":"10.1038/s41585-025-01040-8","DOIUrl":null,"url":null,"abstract":"<p>In vitro data suggest that BRD9 could be a treatment target in testicular germ cell tumours (TGCTs). Inhibition of BRD9 in TGCT cell lines reduced their viability.</p><p>Meta-analysis of Affymetrix microarray data and immunohistochemical analysis showed that BRD9 expression was heterogeneous in TGCT cell lines and patient samples. Treatment of different TGCT cell lines with the BRD9 inhibitor I-BRD9, which is an acetylated lysine mimetic that binds to the bromodomain binding pocket of BRD9, decreased their viability in a time-dependent and a dose-dependent manner. Strong cytotoxic effects were evident in TGCT cell lines, whereas control cell lines were only slightly affected. In TGCT cell lines, I-BRD9 induced apoptosis and cell-cycle arrest in G1 phase. Specifically in embryonal carcinoma cells and seminoma cells, I-BRD9 caused downregulation of pluripotency markers and cell differentiation towards an epithelial cell fate.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"15 1","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Urology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41585-025-01040-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
In vitro data suggest that BRD9 could be a treatment target in testicular germ cell tumours (TGCTs). Inhibition of BRD9 in TGCT cell lines reduced their viability.
Meta-analysis of Affymetrix microarray data and immunohistochemical analysis showed that BRD9 expression was heterogeneous in TGCT cell lines and patient samples. Treatment of different TGCT cell lines with the BRD9 inhibitor I-BRD9, which is an acetylated lysine mimetic that binds to the bromodomain binding pocket of BRD9, decreased their viability in a time-dependent and a dose-dependent manner. Strong cytotoxic effects were evident in TGCT cell lines, whereas control cell lines were only slightly affected. In TGCT cell lines, I-BRD9 induced apoptosis and cell-cycle arrest in G1 phase. Specifically in embryonal carcinoma cells and seminoma cells, I-BRD9 caused downregulation of pluripotency markers and cell differentiation towards an epithelial cell fate.
期刊介绍:
Nature Reviews Urology is part of the Nature Reviews portfolio of journals.Nature Reviews' basic, translational and clinical content is written by internationally renowned basic and clinical academics and researchers. This journal targeted readers in the biological and medical sciences, from the postgraduate level upwards, aiming to be accessible to professionals in any biological or medical discipline.
The journal features authoritative In-depth Reviews providing up-to-date information on topics within a field's history and development. Perspectives, News & Views articles, and the Research Highlights section offer topical discussions and opinions, filtering primary research from various medical journals.
Covering a wide range of subjects, including andrology, urologic oncology, and imaging, Nature Reviews provides valuable insights for practitioners, researchers, and academics within urology and related fields.