Project description:The aim of this investigation was to study the consequences of interfering with soluble epoxide hydrolase (sEH) expression on tumor growth and metastasis in genetically modified animals that spontaneously generate tumors without the exogenous application of high concentrations of epoxide mediators or inhibitors. Therefore, breast cancer development was studied in mice expressing the polyoma middle T oncogene (PyMT) under the control of the mouse mammary tumor virus promoter, to induce spontaneous mammary tumors. To facilitate the study of endogenous sEH activity in tumor growth, PyMT mice were then crossed with sEH-/- mice to generate sEH-deficient mice that spontaneously generate breast tumors (so called PyMTsEH mice). For these analyses, primary tumors were removed from 20 week old mice.
Project description:Breast cancer is a multifaceted disease, exhibiting significant molecular, histological, and pathological diversity. Factors that impact this heterogeneity are poorly understood; however, transformation of distinct normal cell populations of the breast may generate different tumor phenotypes. Our previous study demonstrates that the polyomavirus middle T antigen (PyMT) oncogene can establish diverse tumor subtypes when broadly expressed within mouse mammary epithelial cells. Herein, we assess the molecular, histological, and metastatic outcomes from distinct mammary cell populations transformed with PyMT. By combining several methodologies, including lentiviral infection, cell sorting, and transplantation, we have characterized tumors arising from enriched populations of mammary epithelial cells. We have found that expression of PyMT within different cell populations influences tumor histology, molecular subtype, and metastatic potential. 32 samples, 1 from each of 32 mouse mammary tumors arising from transplanted mouse mamary epithelial cells (MMECs) transduced with PyMT-expressing lentivirus. MMECs were sorted into four different types prior to transplant: luminal CD133+ (8 samples), luminal CD133- (11 samples), stem (6 samples), and basal (7 samples). The background for the cell donor and transplant recipients mice was FVB/NJ obtained from Jackson Laboratories.
Project description:MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in many human diseases including breast cancer. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the roles of miRNAs in association with oncogenic drivers and in specifying sub-types of breast cancer, we performed miRNAexpression profiling on mammary tumors from eight well-characterized genetically -engineered Mouse (GEM) models of human breast cancer including MMTV–H-Ras, -Her2/neu, -c-Myc, -PymT, –Wnt1 and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1fl/fl;p53+/-;MMTV-cre and the p53fl/fl ;MMTV-cre transplant model. As supplementary data miRNA expression data for 3 mouse primary mammary tumors and 8 mouse normal mammary glands from different mouse strains
Project description:MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in many human diseases including breast cancer. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the roles of miRNAs in association with oncogenic drivers and in specifying sub-types of breast cancer, we performed miRNAexpression profiling on mammary tumors from eight well-characterized genetically -engineered Mouse (GEM) models of human breast cancer including MMTV–H-Ras, -Her2/neu, -c-Myc, -PymT, –Wnt1 and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1fl/fl;p53+/-;MMTV-cre and the p53fl/fl ;MMTV-cre transplant model. miRNA expression data for 41 mouse primary mammary tumors and 5 mouse normal mammary glands
