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| 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
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| 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.
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| 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.
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| 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 |
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| Submission date |
Jan 02, 2014 |
| Last update date |
Jan 12, 2017 |
| Contact name |
Valerie Begay |
| E-mail(s) |
vbegay@mdc-berlin.de
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| Organization name |
Max Delbrück Center
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| Street address |
Robert-Rössle-Str. 10
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| City |
Berlin |
| ZIP/Postal code |
13125 |
| Country |
Germany |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA232848 |
| 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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