|
| Status |
Public on Jan 31, 2021 |
| Title |
DIMETHYLBENZANTHRACENE (DMBA) INDUCED MAMMARY CARCINOGENESIS IN MMTV-Neu and MMTV/p53 KO FEMALE MICE AND EFFECTS OF REXINOIDS |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Murine models of mammary cancers have proven to be highly informative on numerous fronts including individual gene causation, microenvironmental analyses, and chemoprevention studies. The MMTV-Neu transgenic model of mammary cancer has proven to be a useful model and has been employed in several prevention studies. However, there are certain practical drawbacks to its use including long tumor latencies and a tendency to develop mutations in the transmembrane domain of Neu (unlike human HER2/Neu overexpressing breast cancers). Here we report modifications that were made in an attempt to optimize this mouse model for chemopreventive screening. First, homozygous MMTV-Neu and homozygous P53 KO mice were crossed to create a MMTV-Neu/P53+/- strain (which more closely approximates the genetic make-up of most HER2+ human patients). Second, to overcome the drawback of long tumor latencies, the mice were treated with DMBA for eight weeks. DMBA treatment greatly decreased the latency of mammary carcinomas in the MMTV-Neu mice although the resulting tumors remained histopathologically similar to those from MMTV-Neu control mice. Next, we examined gene expression in tumors derived from MMTV-Neu, MMTV-Neu/p53+/-, and DMBA treated mice. It was found that the characteristic MMTV-Neu tumor-defined expression pattern was still the most prevalent feature of all the MMTV-Neu tumors despite their being crossed to the p53 null allele, treated with DMBA, or both. However, tumors from the DMBA treated animals exhibited many unique gene expression changes including the high expression of stress response, defense, and inflammation genes. Finally, we demonstrated that the RXR agonists UAB30 and Targretin, both inhibited mammary cancer formation in MMTV-Neu mice, including those treated with DMBA. These results demonstrate the potential utility of this murine model for additional chemoprevention studies.
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| Overall design |
19 samples
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| |
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| Contributor(s) |
Usary J, Perou CM, Lubet RA |
| Citation missing |
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| |
| Submission date |
Jan 18, 2012 |
| Last update date |
Jan 31, 2021 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
cperou@med.unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
|
| Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL2881 |
Agilent-013326 Mouse Oligo Microarray (V2) G4121B (Feature Number version) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
|
| Samples (19)
|
| GSM804346 |
MMTV_ErbB2_p53_Project-0131_10-T11_Grubbs |
| GSM804347 |
MMTV_ErbB2_p53_Project-5811_3-T2_Grubbs |
| GSM804348 |
MMTV_ErbB2_p53_Project-5811_9-T3_Grubbs |
|
| Relations |
| BioProject |
PRJNA165159 |
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