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Series GSE47777 Query DataSets for GSE47777
Status Public on Jun 30, 2013
Title Whole genome expression data comparison between WT and Cebpg-/- MEFs.
Organism Mus musculus
Experiment type Expression profiling by array
Summary C/EBPβ is an important regulator of oncogene-induced senescence (OIS). Here we show that C/EBPγ, a heterodimeric partner of C/EBPβ whose biological functions are not well understood, inhibits cellular senescence. Cebpg-/- MEFs proliferated poorly, entered senescence prematurely, and expressed a pro-inflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBPβ. The senescence-suppressing activity of C/EBPγ required its ability to heterodimerize with C/EBPβ. Covalently linked C/EBPβ homodimers (β~β) inhibited the proliferation and tumorigenicity of RasV12-transformed NIH3T3 cells, activated SASP gene expression, and recruited the CBP co-activator in a Ras-dependent manner, whereas γ~β heterodimers lacked these capabilities and efficiently rescued proliferation of Cebpg-/- MEFs. C/EBPβ depletion partially restored growth of C/EBPγ-deficient cells, indicating that the increased levels of C/EBPβ homodimers in Cebpg-/- MEFs inhibit proliferation. The proliferative functions of C/EBPγ are not restricted to fibroblasts, as hematopoietic progenitors from Cebpg-/- bone marrow also displayed impaired growth. Furthermore, high CEBPG expression correlated with poorer clinical prognoses in several human cancers, and C/EBPγ depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBPγ neutralizes the cytostatic activity of C/EBPβ through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.
Overall design Mouse embryonic fibroblasts were isolated at E13.5 and propagated. At passage 3 cells were plated with equal density and collected 48 hours later.
Contributor(s) Huggins C, Johnson P
Citation(s) 23775115
Submission date Jun 10, 2013
Last update date Feb 11, 2019
Contact name Peter F Johnson
Phone 301 846-1627
Organization name National Cancer Institute
Department Center for Cancer Research
Lab Mouse Cancer Genetics Program
Street address 1050 Boyles St
State/province MD
ZIP/Postal code 21702-1201
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (8)
GSM1159579 WT MEFs at passage 3_biological replicate 1
GSM1159580 WT MEFs at passage 3_biological replicate 2
GSM1159581 WT MEFs at passage 3_biological replicate 3
BioProject PRJNA207798

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Supplementary file Size Download File type/resource
GSE47777_RAW.tar 22.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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