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| Status |
Public on Jun 01, 2010 |
| Title |
Eukaryotic Initiation Factor 4E-BP Protien Family: Sentinels at a Translational Checkpoint in Lung Tumor Defense |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The usurping of translational control by sustained activation of translation initiation factors is oncogenic. Here we show that the primary negative regulators of these oncogenic initiation factors - the 4E-BP protein family - operate as guardians of a translational control checkpoint in tumor defense. When challenged with the tobacco carcinogen NNK, 4ebp1-/-/4ebp2-/- mice showed increased sensitivity to tumorigenesis compared to their wild type counterparts. The 4E-BP deficient state per se creates pro-oncogenic, genome-wide skewing of the molecular landscape - with translational activation of genes governing angiogenesis, growth and proliferation; and translational activation of the precise cytochrome p450 enzyme isoform (CYP2A5) that bioactivates NNK into mutagenic metabolites. Our study provides in vivo proof for a translational control checkpoint in tumor defense.
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| |
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| Overall design |
Comparisons of Total RNA and polysomal RNA from lungs derived from WT and 4ebp1-/-/4ebp2-/- Balb/c mice
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| |
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| Contributor(s) |
Larsson O, Bitterman P |
| Citation(s) |
19843855 |
| Submission date |
Jul 29, 2009 |
| Last update date |
Mar 21, 2012 |
| Contact name |
Ola Larsson |
| E-mail(s) |
ola.larsson@ki.se
|
| Phone |
+46 (0)8 517 73280
|
| Organization name |
Karolinska Institutet
|
| Department |
Department of oncology-pathology
|
| Street address |
CCK, R8:01
|
| City |
Stockholm |
| ZIP/Postal code |
171 76 |
| Country |
Sweden |
| |
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| Platforms (1) |
| GPL5759 |
Affymetrix GeneChip Mouse Genome 430 2.0 Array [CDF: Mm430_Mm_REFSEQ_8] |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA118857 |
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