TGFβ-dependent gene expression shows that senescence correlates with abortive differentiation along several lineages in Myc-induced lymphomas.
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 of 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.
Theodor Boveri Institute, Biocenter, University of Würzburg, Würzburg, Germany.
Judith
J
Müller
Birgit
B
Samans
Jan
J
van Riggelen
Giovanni
G
Fagà
Raquel
R
Peh K N
Chia-Lin
CL
Wei
Heiko
H
Müller
Bruno
B
Amati
Dean
D
Felsher
Martin
M
Eilers
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D016922:Cellular Senescence; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta