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Series GSE53770 Query DataSets for GSE53770
Status Public on Dec 16, 2014
Title Deregulation of the endogenous C/EBPβ LIP isoform predisposes to tumorigenesis
Organism Mus musculus
Experiment type Expression profiling by array
Summary Two long and one truncated isoforms (termed LAP*, LAP,
and LIP, respectively) of the transcription factor CCAAT
enhancer binding protein beta (C/EBPβ) are expressed
from a single intronless Cebpb gene by alternative translation
initiation. Isoform expression is sensitive to mammalian
target of rapamycin (mTOR)-mediated activation of
the translation initiation machinery and relayed through an
upstream open reading frame (uORF) on the C/EBPβ
mRNA. The truncated C/EBPβ LIP, initiated by high
mTOR activity, has been implied in neoplasia, but it was
never shown whether endogenous C/EBPβ LIP may function
as an oncogene. In this study, we examined spontaneous
tumor formation in C/EBPβ knockin mice that constitutively
express only the C/EBPβ LIP isoform from its
own locus. Our data show that deregulated C/EBPβ LIP
predisposes to oncogenesis in many tissues. Gene expression
profiling suggests that C/EBPβ LIP supports a protumorigenic
microenvironment, resistance to apoptosis,
and alteration of cytokine/chemokine expression. The results
imply that enhanced translation reinitiation of C/
EBPβ LIP promotes tumorigenesis. Accordingly, pharmacological
restriction of mTOR function might be a therapeutic
option in tumorigenesis that involves enhanced expression
of the truncated C/EBPβ LIP isoform.
Overall design A cohort of C/EBPb LIP heterozygous (+/L) and wild type (+/+) mice were kept over 25 months and animals showing palpable lymphoma were sacrificed. The lymphoma developed spontaneously. For each genotype, 5 lymphoma were used for RNA preparation and gene expression profiling analysis.
Contributor(s) Begay V, Smink JJ, Loddenkemper C, Zimmermann K, Rudolph C, Scheller M, Steinemann D, Leser U, Schlegelberger B, Stein H, Leutz A
Citation(s) 25401168
Submission date Jan 02, 2014
Last update date Jan 12, 2017
Contact name Valerie Begay
Organization name Max Delbrück Center
Street address Robert-Rössle-Str. 10
City Berlin
ZIP/Postal code 13125
Country Germany
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (10)
GSM1300322 Mouse_20_+/L
GSM1300323 Mouse_40_+/+
GSM1300324 Mouse_866_+/L
BioProject PRJNA232848

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Supplementary file Size Download File type/resource
GSE53770_RAW.tar 91.6 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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