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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 15, 2021 |
| Title |
Progesterone promotes immunomodulation and tumor development in the murine mammary gland |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Clinical studies have linked use of progestins (synthetic progesterone (P4)) to breast cancer risk. However, little is understood regarding the role native P4, signaling through the progesterone receptor (PR), plays in formation of breast tumors. Studies published by our lab highlighted a link between PR and immune signaling pathways, suggesting PR induces PR to repress the interferon signaling pathway. Given these findings, we sought to investigate whether P4/PR drive immunomodulation in the mammary gland and development of mammary gland tumors. We found that mice treated with P4 displayed changes in the mammary gland suggesting inhibited immune response compared to placebo-treated mice. Furthermore, transgenic mice with PR overexpression demonstrated decreased numbers of immune cell populations in their mammary gland, lymph nodes, and spleens. Upon long-term monitoring, we determined that multi-parous PR overexpressing mice developed significantly more mammary gland tumors than control mice. Additionally, tumors of PR overexpressing mice contained fewer infiltrating immune cells. Finally, RNA sequencing analysis of tumor samples revealed that immune-related gene signatures were enriched in tumors of control mice compared to tumors of PR overexpressing mice. Together, these findings provide a novel mechanism behind P4-mediated promotion of mammary gland tumor development and provide rationale to investigate anti-progestin treatment to promote immune-mediated elimination of mammary gland tumors.
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| Overall design |
Total RNA isolated from mammary gland tumors developing in control GAL4 mice and PR/GAL4 mice
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| Contributor(s) |
Hagan CR, Yang HH |
| Citation(s) |
33958486 |
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| Submission date |
Sep 17, 2020 |
| Last update date |
Sep 15, 2021 |
| Contact name |
Howard Yang |
| E-mail(s) |
[email protected]
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| Phone |
2402765257
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| Organization name |
NCI
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| Street address |
9609 Medical Center Dr.
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| City |
Rockville |
| State/province |
MD |
| ZIP/Postal code |
20850 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA664102 |
| SRA |
SRP282878 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158134_RNASeq17FPKM.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE158134_Raw_gene_counts_matrix.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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