Expression data for two primary and two recurrent MTB;TAN-derived tumor cell lines
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ABSTRACT: Baseline gene expression for two primary and two recurrent tumor cell lines derived from MTB;TAN transgenic mice. Microarrays were performed in biological duplicate to determine differential gene expression between primary and recurrent tumor cell cohorts.
Project description:Genome-wide expression data can provide important insights into normal and pathological cellular processes. However, the ability to use gene expression data to quantitatively assess the activation state of a given signaling pathway or transcriptional network in a sensitive and specific manner remains an important unmet goal. We now describe a computational algorithm, energy-paired scoring (EPS), that satisfies these criteria by predicting pathway activity using gene-gene interactions within a pathway signature in a manner analogous to the estimation of energy generated by two charged particles, as described by Coulomb’s law. We demonstrate the ability of EPS to: quantitatively assess pathway activation levels in vivo and in vitro; accurately estimate the extent of pathway inhibition achieved by gene knockdown; sensitively detect crosstalk between endogenous signaling pathways in vivo; and accurately identify compounds capable of inhibiting selected signaling pathways. Our findings indicate that EPS can accurately predict pathway activity over a wide dynamic range based upon gene expression data sets derived from multiple profiling platforms, as well as different species, tissues and cell types in both in vitro and in vivo contexts Four timepoints (0h, 24h, 48h and 96h) with 3 replicates per timepoint of doxycycline induction for MTB (Control), MTB/TAN, MTB/TOM and MTB/TWNT1
Project description:We have previously shown that transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor development in MTB-IGFIR mice. In this study we evaluated whether the miR-200b/200a/429 cluster could also prevent mammary tumor development from a different oncogene, namely Neu/Erbb2. We found that transgenic overexpression of Neu/Erbb2 in MTB-TAN mice induce rapid mammary tumor development and co-overexpression of the miR-200b/200a/429 cluster with Neu/Erbb2 completely prevent mammary epithelial transformation and tumor development
2024-08-26 | GSE270979 | GEO
Project description:Tumor associated macrophage sequencing from primary, regressing, and recurrent MTB TAN tumors.
Project description:Tumor recurrence represents a significant clinical challenge in the treatment and management of breast cancer. To investigate whether copy number aberrations (CNAs) facilitate the re-emergence of tumor growth from residual disease we performed array comparative genomic hybridization (aCGH) on primary and recurrent mammary tumors from an inducible mouse model of type-I insulin-like growth factor receptor (IGF-IR) driven breast cancer. This genome-wide analysis revealed primary and recurrent tumors harbored distinct copy number aberrations (CNAs) with relapsed tumors containing an increased number of gene-level gains and losses. Remarkably, CNAs detected in primary tumors were largely devoid of annotated cancer genes while the vast majority of recurrent tumors harbored at least one CNA containing a known oncogene or tumor suppressor. Specifically, a subset of recurrent tumors carried gains at 6qA2 and 9qA2 which encode the Met and Yap1 oncogenes respectively. The most frequent CNA detected was a focal deletion at 4qC5 involving the Cdkn2a and Cdkn2b tumor suppressor genes. Integrative analysis revealed positive correlations between gene copy number and mRNA expression suggesting Met, Yap1 and Cdkn2a/b may serve as potential driver genes that promote tumor recurrence. Together, these findings indicate that tumor recurrence is facilitated by the acquisition of CNAs with oncogenic potential and provide a framework to dissect the molecular mechanisms that mediate tumor escape from dormancy.
Project description:The tumor heterogeneity between the primary and recurrent hepatocellular carcinoma (HCC) has rarely been explored. The present study aims to illustrate the heterogeneity between the primary and recurrent tumors by integrating multiomic analyses.
Project description:Formalin fixed paraffin embedded (FFPE) primary-recurrent Glioblastoma (pGBM-rGBM) matched patient samples and normal tissue adjacent to tumor (NAT) were analyzed by shotgun DDA proteomics. The proteomic profiles of pGBM-rGBM pairs revealed differentially expressed proteins in rGBM samples, which in future could be used for potential therapeutic interventions.
Project description:Residual disease represents a major obstacle to the successful treatment of breast cancer, however little is known about the biology of residual tumor cells in vivo. To identify genes differentially expressed in vivo in residual tumor cells compared to primary tumor cells or recurrent tumor cells, we used flow cytometry to isolate GFP-labeled tumor cells from primary, residual, or recurrent tumors grown orthotopically in nu/nu mice. WTA was used to amplify RNA from all tumor cells.
Project description:cMET is a well known oncogene whose activation is widely implicated in tumorigenesis and metastasis. To investigate the effects of acute inhibitoin of cMET signaling in the mammary tumors, we inhibited cMET activation in xenograft mammary tumors that were derived from a MET amplified mouse mammary tumor cell line and analyzed the transcriptional alteration between vehicle and MET inhibitor treated tumors.