|
| 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.
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| 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.
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| 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 |
| E-mail(s) |
[email protected]
|
| Phone |
301 846-1627
|
| Organization name |
National Cancer Institute
|
| Department |
Center for Cancer Research
|
| Lab |
Mouse Cancer Genetics Program
|
| Street address |
1050 Boyles St
|
| City |
FREDERICK |
| 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 |
| GSM1159582 |
WT MEFs at passage 3_biological replicate 4 |
| GSM1159583 |
Cebpg-/- MEFs at passage 3_biological replicate 1 |
| GSM1159584 |
Cebpg-/- MEFs at passage 3_biological replicate 2 |
| GSM1159585 |
Cebpg-/- MEFs at passage 3_biological replicate 3 |
| GSM1159586 |
Cebpg-/- MEFs at passage 3_biological replicate 4 |
|
| Relations |
| BioProject |
PRJNA207798 |
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