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| Status |
Public on Jul 15, 2020 |
| Title |
Loss of Fbxw7 triggers mammary tumorigenesis associated with E2F/c-Myc activation and Trp53 mutation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fbw7 is a tumor suppressor protein that regulates the degradation of a multitude of oncogenic substrates, such as c-Jun, c-Myc, Notch1 intracellular domain, and cyclin E. Loss of FBXW7 expression is relatively common in breast cancer. Despite this, the effect of FBXW7 loss on breast tumorigenesis has not been examined. We demonstrate here that loss of FBXW7 is sufficient for breast tumorigenesis. Many of Fbw7’s substrates are transcription factors or are closely linked to transcription factor pathways. As loss of Fbw7 results in upregulation of multiple substrates, we set out to determine which, if any of these transcription factor pathways predominate early after Fbw7 loss and after tumorigenesis. To address this, we employed genome-wide RNA sequencing to examine transcription factor pathway alterations early after FBXW7 loss in non-tumor breast epithelial cells as well as after prolonged FBXW7 loss, in tumor samples. We demonstrate an early upregulation of E2F and c-Myc pathways that is reinforced upon tumorigenesis. These findings suggest E2F and c-Myc as important targetable pathways in Fbw7 low breast cancer patients.
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| Overall design |
RNA-seq of 4 conditions, 1-6 replicates of each
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| Contributor(s) |
Alison M, Quinlan F, Cary S, Alex M, Sridhar R |
| Citation(s) |
33070870 |
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| Submission date |
Feb 03, 2020 |
| Last update date |
Nov 02, 2020 |
| Contact name |
Sridhar Rao |
| E-mail(s) |
[email protected]
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| Phone |
4149373841
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| Organization name |
BloodCenter of Wisconsin
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| Department |
Blood Research Institute
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| Street address |
8727 Watertown Plank Road
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| City |
Milwaukee |
| State/province |
WI |
| ZIP/Postal code |
53226 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (13)
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| GSM4293861 |
Fbw7+/+ epithelials, nontumor 076_epithelial |
| GSM4293862 |
Fbw7-/- epithelials, nontumor 016_epithelial |
| GSM4293863 |
Fbw7-/- epithelials, nontumor 042_epithelial |
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| Relations |
| BioProject |
PRJNA604590 |
| SRA |
SRP246915 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144690_SecondRunAnalysis.txt.gz |
629.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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