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| Status |
Public on Dec 29, 2014 |
| Title |
Her2/Neu tumorigenesis and metastasis is regulated by E2F transcription factors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
HER2 / Neu is amplified and overexpressed in a large proportion of human breast cancers, but the signaling pathways that contribute to tumor development and metastatic progression are not completely understood. Using gene expression data and pathway signatures we predicted a role for activator E2F transcription factors in Neu induced tumors. This was genetically tested by interbreeding Neu transgenics with knockouts of the three activator E2Fs. Loss of any E2F delayed Neu induced tumor onset. E2F1 loss accelerated tumor growth while E2F2 and E2F3 loss did not. Strikingly, it was observed that loss of E2F1 or E2F2 significantly reduced the metastatic capacity of the tumor and this was associated with a reduction in circulating tumor cells in the E2F2 knockout. Gene expression analysis between the tumors in the various E2F mutant backgrounds revealed that there was extensive compensation by other E2F family members in the individual knockouts, underscoring the importance of the E2Fs in HER2 / Neu induced tumors. Extension to HER2 positive human breast cancer revealed a number of HER2+ subtypes based on E2F activity with differences in relapse free survival times. Taken together these data demonstrate that the E2F transcription factors are integral to HER2+ tumor development and progression.
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| Overall design |
MMTV-Neu tumors in a wild type E2F background and E2F1 knockout, E2F2 knockout and E2F3 +/- backgrounds were analyzed for their gene expression changes.
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| Contributor(s) |
Andrechek ER |
| Citation(s) |
24362522, 37805590 |
| |
| Submission date |
Nov 27, 2012 |
| Last update date |
Oct 20, 2023 |
| Contact name |
Eran Andrechek |
| Phone |
517-884-5042
|
| Organization name |
Michigan State University
|
| Department |
Physiology
|
| Lab |
Andrechek
|
| Street address |
2120 BPS Building
|
| City |
East Lansing |
| State/province |
MI |
| ZIP/Postal code |
48824 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA182217 |
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