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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 05, 2010 |
| Title |
An Ets2-specific transcriptional program in tumor-associated macrophages promotes metastasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes.
Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung.
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| Overall design |
Breast TAMs were isolated from early-stage PyMT-induced mammary tumors expressing Ets2 and also from the tumors with Ets2-deficient TAMs. Since macrophages have also been implicated in normal mammary gland remodeling, normal remeodeling macrophages were also purified from females expressing Ets2 and the ones where Ets2 is deleted in the macrophages. One RNA sample was extracted from each genetic group for gene-expression profiling.
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| Contributor(s) |
Zabuawala T, Taffany DA, Sharma SM, Merchant A, Adair B, Srinivasan R, Rosol TJ, Fernandez S, Huang K, Leone G, Ostrowski MC |
| Citation(s) |
20145133 |
| Submission date |
Sep 19, 2008 |
| Last update date |
May 04, 2018 |
| Contact name |
Michael Ostrowski |
| E-mail(s) |
Michael.Ostrowski@osumc.edu, zabuawala.1@osu.edu
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| Organization name |
Ohio State University
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| Street address |
460 W 12th Ave
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| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43210 |
| Country |
USA |
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| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA111101 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12863_RAW.tar |
8.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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