Project description:We aimed to understand the transcriptome patterns of organ-derived cancer cell isolates from MMTV-PyMT mice. Tissues from primary tumors and organs harboring distal metastases were harvested from cancer bearing female mice. Although metastatic progression from primary tumors to lung tissue is well studied in the MMTV-PyMT model, metastases to other distal organs and the significance of intratumor heterogeneity across metastases from distal organs remain unclear. To gain insight, we established an array of metastatic cell lines harvested from the MMTV-PyMT breast cancer mouse model. Sequencing at bulk and single-cell level were performed and used to examine the effects of cell heterogeneity on metastases and organ tropism
Project description:In order to identify transciptomic changes of endothelial cells (Ecs) in response to STING activation, endothelial cells were soted using FACS and RNA-seq was performed. We compared ECs from 3 models; normal mammary fat pad, MMTV-PyMT spontaneous breast tumor, implanted breast tumor. Tumor cells derived from MMTV-PyMT spontaneous breast tumor were expanded on culture and implanted in mammary fat pad of female FVB mice to establish implanted breast tumor model.
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:Dipyridamole (DPM) is widely used to prevent strokes and vascular thrombosis. Combination therapy of DPM and antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter driven polyoma middle T oncoprotein (MMTV-PyMT) metastatic breast cancer model. We also investigated the effects of DPM on gene and miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary tumor growth kinetics and the number of lung metastases in transgenic mice treated with DPM or vehicle. Gene expression and microRNA (miRNA) expression profiles of mammary tumor tissues were then analyzed using the Affymetrix GeneChipM-BM-. or miRNA 2.0 arrays. Real-time quantitative PCR (qPCR) was used to confirm changes in gene expression. Treatment with DPM beginning at the age of four weeks delayed the onset of palpable lesions, delayed tumor progression and suppressed lung metastasis. Microarray gene expression analysis identified 253 genes differentially expressed between DPM-treated and control mammary tumors. miRNA expression analysis revealed that 53 miRNAs were altered by DPM treatment. The results indicate that DPM has chemoprevention activity against breast cancer tumorigenesis and metastasis in mice. The array analyses provide insights into potential mechanisms of DPMM-bM-^@M-^Ys chemopreventive effects, involving upregulation of several genes and miRNAs known to suppress cancer growth and/or metastasis and downregulation of genes known to promote cancer. Some of these genes have not been previously studied in breast cancer and may serve as novel molecular targets for breast cancer chemoprevention. MMTV-PyMT+ female mice were randomly divided into a DPM treatment group (n=10 mice, total of 100 glands) and a vehicle (control) group (n=7 mice, total of 70 glands). When mice were four weeks old, when hyperplasia lesions begin to develop in the FVB strain (21), DPM (10 mg/kg) or vehicle was injected IP into the peritoneum of each mouse on a 5 days on/2 days off dosing schedule for a total of 11 weeks (week one=injection one), until mice were 15 weeks of age. Each of the 10 mammary tumors per mouse was monitored until the study end point. A total six breast tumor RNA samples were used for microarray analysis, with three form mice treated with DPM and three from mice treated with vehicle.
Project description:Purpose: The goals of this study are to compare transcriptome (RNA-seq) differences between wild type and mutant Bad using MMTV-PyMT mouse breast cancer model. Methods: MMTV-PyMT breast cancer model tumors samples (6 independent mice for each genotype) were RNA-sequenced. Reads quality control and alignment to reference genome was done using fastp and STAR aligner respectively. Differentially expressed genes (DEGs) were computed using DESeq2.
Project description:The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) loss on the gene expression profiles of tumors from MMTV-Polyomavirus middle-T antigen (PyMT) mice. MMTV-PyMT/S14-heterozygous mice were crossed with S14-heterozygous mice and 1 cm tumors from MMTV-PyMT control (wild-type S14) or MMTV-PyMT/S14-null offspring were profiled using Affymetrix gene arrays. Tumor latency was not different between groups; however, tumors lacking S14 grew significantly slower than control tumors. Loss of S14 also decreased the levels of de novo synthesized fatty acids in mammary tumors. In additional studies, performed on MMTV-Neu mice, we found that S14 overexpression was associated with increased tumor cell proliferation and elevated levels of tumor fatty acids. Gene expression profiling revealed that S14 loss and overexpression in mouse mammary tumors altered pathways associated with proliferation and metabolism. This study provides important information about the role of S14 in mammary tumorigenesis and tumor metabolism. Microarray analysis was performed on 4 mammary tumors from MMTV-PyMT mice and 4 tumors from MMTV-PyMT/S14-null mice.
Project description:MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs), controlling genes involved in a variety of cellular processes. miRNA dysregulation is recognized to play an essential role in the development and progression of cancer. MMTV-PyMT mice (Jax Strain: FVB/N-Tg(MMTV-PyVT)634Mul/J) are a well-characterized transgenic mouse model of breast cancer. Upon activation of the MMTV-PyVT transgene (mouse mammary tumor virus (MMTV) long terminal repeat upstream of a cDNA sequence encoding the Polyoma Virus middle T antigen (PyVT)) female carriers develop palpable mammary tumors as early as 5 weeks of age. We performed miRNA microarrays on samples from the MMTV-PyMT transgenic mouse model to investigate the differential expression of miRNAs during development of malignant disease in this model.
Project description:In this study, radiation therapy was performed on mouse breast cancer spontaneous gene mice (MMTV-PyMT) to obtain radiation therapy model of breast cancer mice. To simulate clinical breast cancer radiotherapy and study the differential proteins of breast cancer radiotherapy resistance. MMTV-PyMT mice were randomly divided into two groups, and the radiotherapy group was given the same dose 5 times (3GY, once every 2 days) when the breast cancer tumor grew to an appropriate size (200mm3). The protein extracted from mouse tumor was analyzed by mass spectrometry.
Project description:Mice have been used as models for human breast cancers for many years, however, it is still unclear which murine models faithfully represent human tumor phenotypes. To address this question, we used DNA microarrays to characterize 10 different murine mammary models and compared these data to the expression patterns from primary human breast tumors. Hierarchical clustering analysis of the murine samples showed that the WAP-Myc, MMTV-Neu, MMTV-PyMT, WAP-Int3, and C3(1)-Tag tumors were highly correlated within each model. Other models, including the WAP-T_121 , MMTV-Wnt1, and DMBA-induced tumor model, did not show this consistency and gave rise to tumors with potentially different cell types of origin. A combined clustering analysis of the murine tumors with 102 human breast tumors showed many shared expression features. These features included a proliferation signature, an Interferon-regulated pattern, and patterns reflective of the presence of lymphocytes and fibroblasts. Murine tumors could be categorized according to their presumed cellular origins; the C3(1)-Tag, BRCA1+/-; p53+/-;IR, and DMBA-treated models displayed expression characteristics of human basal-like breast tumors; the MMTV-Neu, MMTV-PyMT, and WAP-Myc models shared features with human luminal breast tumors including the high expression of GATA3 and XBP1. In some cases, single mouse models did not reproduce the entire expression pattern seen in a specific human subtype; rather portions of a subtype’s expression profile were captured/represented by different murine models. The presence of shared patterns of expression between mice and humans provides a common framework for the direct comparison and integration of animal models with human breast Keywords: reference x sample
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).