Project description:S100A10 (p11) is a plasminogen receptor that regulatess cellular plasmin generation by cancer cells. In the current study we used the MMTV-PyMT mouse breast cancer model to investigate the role of p11 in oncogenesis. Genetic deletion of p11 resulted in significantly decreased tumor onset, growth rate and spontaneous pulmonary metastatic burden in the PyMT/p11-KO mice. This phenotype was accompanied by substantial reduction in Ki67 positivity, macrophage infiltration and decreased vascular density in the primary tumors, and appearance of invasive carcinoma and pulmonary metastasis. Surprisingly, immunohistochemical analysis of wild-type MMTV-PyMT mice failed to detect p11 expression in the tumors or metastatic tumor cells and loss of p11 did not decrease plasmin generation in the PyMT tumors and cells. Furthermore, tumor cells expressing p11 displayed dramatically reduced lung metastasis when injected into p11-depleted mice, further strengthening the stromal role of p11. Transcriptome analysis of the p11-depleted tumors showed marked reduction in genes involved in breast cancer development, progression, and inflammation such as AREG, MUC1 and S100A8. The PyMT/p11-KO tumors displayed remarkable increase in inflammatory cytokines such as IL-6, IL-10 and IFN-γ. Gene expression profiling and immunohistochemistry primary breast cancer samples showed that p11 mRNA and protein was significantly higher in tumors compared to normal mammary tissue. The mRNA expression was significantly associated with poor patient prognosis and significantly elevated in high grade, triple negative tumors and tumors with high proliferative index. We used microarray to detail the global programme of gene expression underlying reduced growth/establishment of P11-KO PyMT tumours.
Project description:Previously, lncRNA Malat1 knockout mice were generated by insertional inactivation. By crossing this line to MMTV-PyMT mammary tumor mouse model, we produced PyMT;Malat1 wild-type (WT) and PyMT;Malat1 knockout (KO). Furthermore, we generated Malat1 transgenic mice by targeting ROSA26 locus and bred them to PyMT;Malat1 knockout mice to produce Malat1-rescued PyMT;Malat1 knockout;Malat1 transgenic animals (TG). Using mammary tumors from the three groups of animals, we performed RNA-Seq analysis to identify differentially up-regulated genes in KO tumors to find novel target genes of YAP-TEAD pathway.
Project description:Here, we use single cell sequencing to delineate the heterogeneity of tumours from the genetically engineered MMTV-PyMT mouse model of breast cancer (MMTV-PyMT::K14Cre::Rosa-tdTomato mice).
Project description:We compared the transcriptional profile of mammary tumors spontaneously developed in PyMT transgenic mice either bearing or not additional copies of the endogeneous SIRT6 gene.
Project description:To investigate the role of NR1D1 in the progression of breast cancer, mammary gland tumor tissues were obtained from 14 weeks old FVB Nr1d1+/+;PyMT and Nr1d1-/-;PyMT mice and the gene expression patterns were analyzed by RNA-seq.
Project description:To characterise the metabolic landscape of metastatic breast cancer we investigated differences in metabolites between the serum of MMTV-PyMT (Mouse Mammary Tumor Virus long terminal repeat upstream of a cDNA sequence encoding the Polyoma Virus middle T antigen) mice and their wild-type counterparts (https://doi.org/10.1101/2024.07.02.601676). Here we provide matched transcriptomic data on the primary mammary tumors from MMTV-PyMT mice and the mammary gland from FVB/N mice
Project description:The goal of this study is to characterize and compare endothelial cell populations within PyMT mammary tumors exhibiting distinct tumor immune microenvironments. Using single-cell RNA sequencing of endothelial-enriched tumor samples, this dataset enables systematic comparison of endothelial transcriptional states between PyMT-M and PyMT-N tumors. The study is designed to provide a resource for investigating tumor-associated vascular heterogeneity and endothelial remodeling in the PyMT mouse model.
Project description:We labeled PyMT control cells versus PyMT-GPx2 KD with GFP in vitro and then injected into mammary fat pad of mice for incubating 45 days. We then generated single cell suspension by FACS sorting from PyMT-control, GPx2 KD. 10X Genomics was used to make cDNA library. We then sequenced the samples with Illumina high throughput sequencing.