TGFbeta-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages in Myc-induced lymphomas

Judith Müller, Birgit Samans, Jan Van Riggelen, Giovanni Fagà, K. N. Raquel Peh, Chia Lin Wei, Heiko Müller, Bruno Amati, Dean Felsher, Martin Eilers

Research output: Contribution to journalArticle

Abstract

Deregulated expression of Myc under the control of an immunoglobulin enhancer induces lymphoma formation in mice. The development of lymphomas is limited by TGFβ-dependent senescence and high levels of Myc expression are continuously required to antagonize senescence. The biological processes underlying senescence are not fully resolved. We report here a comprehensive analysis of TGFβ-dependent alterations in gene expression when the Myc transgene is switched off. Our data show that Myc-induced target genes are down-regulated in a TGFβ-independent manner. In contrast, TGFβ is required to upregulate a broad spectrum of genes that are characteristic for different T-cell lineages when Myc is turned off. The analysis reveals a significant overlap between these Myc-repressed genes with genes that are targets of polycomb repressive complexes in embryonic stem cells. Therefore, TGFβ-dependent senescence is associated with gene expression patterns indicative of abortive cellular differentiation along several lineages.

Original languageEnglish
Pages (from-to)4622-4626
Number of pages5
JournalCell Cycle
Volume9
Issue number23
DOIs
Publication statusPublished - Dec 1 2010

Keywords

  • Lymphoma
  • Myc
  • Polycomb
  • Senescence
  • TGFβ

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology
  • Medicine(all)

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