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  Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphoma-genesis via Suv39h1-Dependent Senescence

Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., et al. (2010). Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphoma-genesis via Suv39h1-Dependent Senescence. Cancer Cell, 17, 262-272. doi:10.1016/j.ccr.2009.12.043.

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 Urheber:
Reimann, Maurice1, Autor
Lee, Soyoung1, Autor
Loddenkemper, Christoph1, Autor
Dörr, Jan R.1, Autor
Tabor, Vedrana1, Autor
Aichele, Peter1, Autor
Stein, Harald1, Autor
Dörken, Bernd1, Autor
Jenuwein, Thomas2, Autor           
Schmitt, Clemens A.1, Autor
Affiliations:
1External Organizations, ou_persistent22              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 Zusammenfassung: Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR). In contrast, Myc activation-although producing a DDR as well-is known to primarily elicit an apoptotic countermeasure. Using the Eμ-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic lymphoma cells activate macrophages to secrete transforming growth factor β (TGF-β) as a critical non-cell-autonomous inducer of cellular senescence. Accordingly, neutralization of TGF-β action, like genetic inactivation of the senescence-related histone methyltransferase Suv39h1, significantly accelerates Myc-driven tumor development via cancellation of cellular senescence. These findings, recapitulated in human aggressive B cell lymphomas, demonstrate that tumor-prompted stroma-derived signals may limit tumorigenesis by feedback senescence induction.

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Sprache(n): eng - English
 Datum: 2010-03-16
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.ccr.2009.12.043
 Art des Abschluß: -

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Titel: Cancer Cell
  Andere : Cancer Cell
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Cambridge, Mass. : Cell Press
Seiten: - Band / Heft: 17 Artikelnummer: - Start- / Endseite: 262 - 272 Identifikator: ISSN: 1535-6108
CoNE: https://pure.mpg.de/cone/journals/resource/111025129473004