dc.contributor.author | Wacker, Ingrid | |
dc.contributor.author | Sachs, Martin | |
dc.contributor.author | Knaup, Karl | |
dc.contributor.author | Wiesener, Michael | |
dc.contributor.author | Weiske, Joerg | |
dc.contributor.author | Huber, Otmar | |
dc.contributor.author | Behrens, Juergen | |
dc.contributor.author | Akçetin, Ziya | |
dc.date.accessioned | 2022-05-11T14:36:56Z | |
dc.date.available | 2022-05-11T14:36:56Z | |
dc.date.issued | 2009 | |
dc.identifier.issn | 0270-7306 | |
dc.identifier.issn | 1098-5549 | |
dc.identifier.uri | https://doi.org/10.1128/MCB.01184-07 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11776/8490 | |
dc.description.abstract | The von Hippel-Lindau tumor suppressor gene (VHL) is mutated in clear cell renal cell carcinomas (RCC), leading to the activation of hypoxia-inducible factor (HIF)-mediated gene transcription. Several VHL/HIF targets, such as glycolysis, angiogenesis, cell growth, and chemotaxis of tumor cells, have been implicated in the transformed phenotype of RCC-regulating properties. Here, we show that VHL suppresses key features of cell transformation through downregulation of the HIF-dependent expression of activin B, a member of the transforming growth factor beta superfamily. Activin B expression is repressed by restoration of VHL in VHL-deficient RCC cells and upregulated by hypoxia. RCC tumor samples show increased expression of activin B compared to that in the normal kidney. VHL increases cell adhesion to the extracellular matrix, promotes cell flattening, and reduces invasiveness. These effects are completely phenocopied by RNA interference-mediated knockdown of activin B and reverted by treatment with recombinant activin B. Finally, knockdown of activin B reduces tumor growth of RCC cells in nude mice. Our data indicate that activin B is a key mediator of VHL/HIF-induced transformation in RCC. | en_US |
dc.description.sponsorship | Sonderforschungsbereich 423 of the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) | en_US |
dc.description.sponsorship | We thank P. Ratcliffe for providing the RCC4 and the RCC4 VHL + cells, W. Kaelin for providing the 786.0 and the 786.0 VHL + cells, K. von der Mark for gifts of reagents and for helpful discussions, and E. Schefler for technical assistance.; This work was supported by a grant from Sonderforschungsbereich 423 of the Deutsche Forschungsgemeinschaft to J.B. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Amer Soc Microbiology | en_US |
dc.identifier.doi | 10.1128/MCB.01184-07 | |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Renal-Carcinoma Cells | en_US |
dc.subject | E-Cadherin | en_US |
dc.subject | Gene-Product | en_US |
dc.subject | Vhl | en_US |
dc.subject | Invasion | en_US |
dc.subject | Cancer | en_US |
dc.subject | Growth | en_US |
dc.subject | Differentiation | en_US |
dc.subject | Morphogenesis | en_US |
dc.subject | Metastasis | en_US |
dc.title | Key Role for Activin B in Cellular Transformation after Loss of the von Hippel-Lindau Tumor Suppressor | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Molecular and Cellular Biology | en_US |
dc.department | Fakülteler, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Üroloji Ana Bilim Dalı | en_US |
dc.authorid | 0000-0003-4359-1747 | |
dc.authorid | 0000-0003-1803-4463 | |
dc.identifier.volume | 29 | en_US |
dc.identifier.issue | 7 | en_US |
dc.identifier.startpage | 1707 | en_US |
dc.identifier.endpage | 1718 | en_US |
dc.institutionauthor | Akçetin, Ziya | |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.authorscopusid | 6603453628 | |
dc.authorscopusid | 55126435700 | |
dc.authorscopusid | 6506303174 | |
dc.authorscopusid | 6603460548 | |
dc.authorscopusid | 6508214213 | |
dc.authorscopusid | 7005830805 | |
dc.authorscopusid | 6602118986 | |
dc.authorwosid | Huber, Otmar/AAA-4548-2021 | |
dc.identifier.wos | WOS:000264080900004 | en_US |
dc.identifier.scopus | 2-s2.0-63049111496 | en_US |
dc.identifier.pmid | 19158274 | en_US |