Project description:We performed affymetrix gene expression profiling on mammary tumors from eight well-characterized genetically engineered Mouse (GEM) models of human breast cancer. The gene expression data will be combined with the miRNA gene expression data from the corresponding mammary tumors and tissues for integrated miRNA and mRNA gene expression analysis, which are useful in improving the identification of miRNA targets from potential targets identified in silico. mRNA expression data for 41 mouse primary mammary tumors and 5 mouse normal mammary glands
Project description:We performed affymetrix gene expression profiling on mammary tumors from eight well-characterized genetically engineered Mouse (GEM) models of human breast cancer. The gene expression data will be combined with the miRNA gene expression data from the corresponding mammary tumors and tissues for integrated miRNA and mRNA gene expression analysis, which are useful in improving the identification of miRNA targets from potential targets identified in silico.
Project description:This study presents exon array expression data for multiple mammary tumor cell lines derived from various genetically-engineered mouse models of mammary cancer as well as from cell lines derived from spontaneously arising mouse mammary tumors.
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
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:Background: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models (GEMMs) are useful resources for studying breast cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and improve preclinical drug validation. Results: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes (classes). Across species analyses using three independent human breast cancer datasets identified eight murine classes that represent specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWap-Myc, and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathways between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis and candidate pathways for therapeutic intervention. Conclusion: This study consolidates murine models of breast carcinoma into the largest comprehensive transcriptomic dataset to date to identify human-mouse disease subtype counterparts. This approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple GEMMs are needed to represent the diversity of human breast cancers. These trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of the human disease subtypes are used. Keywords: breast cancer, comparative genomics, genetically engineered mouse models, and molecular pathway signatures reference x sample
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines that metastasize in syngeneic mouse hosts and we have assessed gene expression programs in the untreated primary tumors with the goal of generating information that may be useful to the identification of biomarkers that predict response to therapeutic intervention. We used microarrays to assess global gene expression programs in primary tumors from 12 metastatic mouse mammary tumor models transplanted orthotopically into syngeneic, fully immunocompetent mouse hosts. The 12 tumor models used here are based on published cell lines that had been established from either spontaneous mammary tumors or from mammary tumors arising in genetically engineered mouse models. All cell lines were previously described to be metastatic. Cells were surgically implanted in the #4 mammary fat pads of syngeneic mice and primary tumors were harvested when they reached 0.5-1.0 cm diameter and snap-frozen for later RNA extraction. 4 independent tumors were collected for each of the 12 models.
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines derived from spontaneously-arising mouse mammary tumors or from mammary tumors arising in genetically engineered mouse models. We used the Affymetrix Mouse Diversity Genotyping Array to address DNA copy number variation in the genomes of the cell lines of this panel. The resulting information about regions of amplification and deletion should help inform biological analyses as well as provide a reference for cell line authentication/identification. Affymetrix Mouse Diversity Genotyping arrays were used according to manufacturer's directions to analyze gDNA extracted from 27 mouse mammary cell lines of varying malignancy.