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

 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 downregulated in a TGFβ-independent manner. In contrast, TGFβ is required to upregulate a broad spectrum of genes that are characteristic for differenT-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.

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4622 - 4626
doi
10.4161/cc.9.23.14211
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TGFβ-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages in Myc-induced lymphomas