Project description: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.
Project description:Transcriptional profiling of mammary gland tumors from transgenic mice overexpressing the p110 or p75 isoform of CUX1. RNA was extracted from epithelial cells isolated using Laser-Capture Microdissection (LCM)
Project description:The main goal of this experiment was to contrast the gene expression of mammary gland tissues at three different tumoral stages : M/D-driven mammary gland small tumors vs mammary gland tissues that have been exposed to M/D but they did not develop a tumor (hyperplastic mammary gland) vs mammary gland tissues that were NOT expossed to M/D (normal mammary gland). Expression profile of 18 mice mammary gland tissues at 3 differents neoplastic stages before and after M/D expossure
Project description:WT mammary gland(WTMG),mutant-MG(MTMG),WT breast tumors(WTBT),MTBT and MTBT-adjacent MG were collected to do data-independent acquisiton(DIA)mass to find the intrinsic factors that is associated with Brca1-deficiency induced breast cancer.
Project description:WT mammary gland(WTMG),mutant-MG(MTMG),WT breast tumors(WTBT),MTBT and MTBT-adjacent MG were collected to do data-independent acquisiton(DIA)mass to find the intrinsic factors that is associated with Brca1-deficiency induced breast cancer.
Project description:Transcriptional profiling of mammary gland tumors from transgenic mice overexpressing the p110 or p75 isoform of CUX1. RNA was extracted from epithelial cells isolated using Laser-Capture Microdissection (LCM) 9 tumors from p75-CUX1 transgenic mice and 8 tumors from p110-CUX1 mice. Biological samples were hybridized in technical duplicates with dye swaps between duplicates against a common reference for normalization.