Mouse mammary tumor-initiating cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE8863 | GEO | 2008/06/27
SECONDARY ACCESSION(S): PRJNA102225
REPOSITORIES: GEO
Similar Datasets
Project description:Using a syngeneic p53 null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified by limiting dilution transplantation as well as in vitro mammosphere and clonogenic assays a Lin-CD29HighCD24High subpopulation of tumor-initiating cells. Differentially expressed genes in the Lin-CD29HighCD24High mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. Experiment Overall Design: The cells were labeled (for FACS sorting) with CD29 and CD24 antibodies, and 4 subpopulations were collected (CD29HighCD24High, CD29HighCD24Low,CD29LowCD24High, and CD29LowCD24Low) to do either in vivo transplantation or to isolate RNA from each of them for array to correlate the in vivo data. Experiment Overall Design: 12 samples (RNA of 4 subpopulations based on expression of CD29 and CD24 for each tumor of 3) were included in the identification of differentially expressed genes of tumor-initiating cells. 5 samples (RNA of subpopulations based on expression of CD29 and CD24 of normal mammary epithelial cells ) were included in the normal group analysis. Reference RNA was used to normalize all samples.
2008-10-18 | E-GEOD-8863 | biostudies-arrayexpress
Project description:CCAAT/enhancer binding protein beta (C/EBPb) is a member of a family of highly conserved transcription factors that regulates numerous genes involved in proliferation and differentiation in a variety of tissues. C/EBPb is deregulated in human breast cancer and germline deletion of this gene results in multiple defects in mammary gland development. We hypothesized that C/EBPb regulates mammary stem cell self-renewal, maintenance and/or differentiation through the regulation of multiple target genes that coordinate mammary gland development. Utilizing both a germline knockout mouse model and a conditional knockout strategy, we demonstrated that mammosphere formation was significantly decreased in C/EBPb-deficient mammary epithelial cells (MECs). The ability of C/EBPb-deleted MECs to regenerate the mammary gland in vivo was severely impaired when transplanted at limiting dilution. Furthermore, serial transplantation of C/EBPb-null mammary tissue resulted in decreased outgrowth potential when compared to wildtype, and an early senescence phenotype. Flow cytometric analysis revealed that C/EBPb-null MECs contain a lower frequency of repopulating stem cells accompanied by an increase in committed, differentiated luminal cells as compared to wildtype. Microarray analysis of stem/progenitor cell populations was performed and revealed an alteration in cell fate specification in C/EBPb-null glands, exemplified by the aberrant expression of basal markers in the luminal cell compartment. Collectively, our studies demonstrate that C/EBPb is a critical regulator of mammary stem cell differentiation, and an important determinant of luminal cell fate specification. Experiment Overall Design: To identify potential signaling pathways regulated by C/EBPb in stem/progenitor cells, microarray analysis was performed on two stem/progenitor cell subpopulations. For this analysis, subpopulations defined by LIN-CD24+CD29hi and LIN-CD24hiCD29lo were FACS sorted from wildtype and germline C/EBPb-/- glands, and RNA was isolated from each group.
2010-02-05 | E-GEOD-16380 | biostudies-arrayexpress
Project description:In the past few years, mammary cancer initiating cells (CICs) have been identified in mouse and human as a subpopulation of tumor cells that selectively posses tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of non-tumorigenic cancer cells progeny through differentiation. They could also be responsible for tumor progression, metastasis, resistance to therapy and recurrence. Thus, the understanding of the pathways regulating CIC self-renewal, differentiation and tumorigenicity represents an important task in the development of effective anticancer therapies. To detect the set of genes associated to CIC in our mouse breast cancer model we analysed three prototypic situations: TUBO cells grown in DMEM under adherent conditions (called TDA in GSE26517 and epithelial bulk in GSE21451), TUBO cells grown in mammosphere medium under adherent conditions (called TMA in GSE26517), TUBO cells grown in mammosphere medium under low-attachment conditions (called mammospheres p1 in GSE21451), i.e. the conditions used to support the formation of mammospheres. This analysis led to the identification of growth factors and immune system-related genes, including toll-like receptor 2 (TLR2). The inhibition of TLR2 signaling pathway strongly impaired mammosphere generation, demonstrating the involvement of TLR2 in CSC self-renewal.
2013-11-30 | GSE26527 | GEO
Project description:In the past few years, mammary cancer initiating cells (CICs) have been identified in mouse and human as a subpopulation of tumor cells that selectively posses tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of non-tumorigenic cancer cells progeny through differentiation. They could also be responsible for tumor progression, metastasis, resistance to therapy and recurrence. Thus, the understanding of the pathways regulating CIC self-renewal, differentiation and tumorigenicity represents an important task in the development of effective anticancer therapies. To detect the set of genes associated to CIC in our mouse breast cancer model we analysed three prototypic situations: TUBO cells grown in DMEM under adherent conditions (called TDA in GSE26517 and epithelial bulk in GSE21451), TUBO cells grown in mammosphere medium under adherent conditions (called TMA in GSE26517), TUBO cells grown in mammosphere medium under low-attachment conditions (called mammospheres p1 in GSE21451), i.e. the conditions used to support the formation of mammospheres. This analysis led to the identification of growth factors and immune system-related genes, including toll-like receptor 2 (TLR2). The inhibition of TLR2 signaling pathway strongly impaired mammosphere generation, demonstrating the involvement of TLR2 in CSC self-renewal. We profiled on MouseWG?6 v2.0 Illumina beadchips two independent experiments: ADHERENT (GSE26517) made by the comparison between TDA and TMA and SOSPENSION (part of GSE21451) made by the comparison between epithelial bulk and mammospheres p1. Mammosphere medium contains epidermal growth factor (EGF), insulin and basic fibroblast growth factor (bFGF) that may influence transcript expression in a way not necessarily related to the assembly of mammospheres. Therefore, following normalization and removal of those transcripts not expressed and not changing, we used the Integrative Correlation coefficient (IC, Parmigiani et al. Clin Cancer Res 2004, 10:2922–2927) as filter to remove genes only associate to growth factors present in the mammosphere medium under adherent growth conditions, i.e IC > 0.1. Differential gene expression was then assessed by regularized t?test (Smyth GK. Stat Appl Genet Mol Biol 2004, 3:Article3) comparing mammospheres p1 with respect to epithelial bulk, using an uncorrected p-value ? 0.05, together with an absolute log2 fold change threshold ?1.
2013-11-30 | E-GEOD-26527 | biostudies-arrayexpress
Project description:The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor). We used microarrays to detect differentially expressed genes in the TIC fraction compared to the non-TIC fraction of the same tumor
2011-05-28 | GSE29590 | GEO
Project description:The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor). We used microarrays to detect differentially expressed genes in the TIC fraction compared to the non-TIC fraction of the same tumor Cells from each primary tumor were separated by FACS into TIC and non-TIC fractions and total RNA was extracted and hybridized on Affymetrix microarrays.
2011-05-28 | E-GEOD-29590 | biostudies-arrayexpress
Project description:NOTCH activation has been recently implicated in human basal-like breast cancers associated with a poor prognosis. To address the role of Notch1 in mammary transformation and mammary tumor initiating cell activity, we developed a doxycycline-regulated model of Notch1-mediated mammary transformation. These mice develop mammary adenocarcinomas that express cytokeratin (CK) 8/18 and contain rare cells that also express keratin 14. In vivo limiting dilution analyses reveal that these mammary tumors exhibit functional heterogeneity and harbor a rare (1/2978) mammary tumor initiating cell population. Using this dox-regulated Notch1 mammary tumor model, we demonstrate that Notch1 inhibition results in mammary tumor regression in vivo and prevents disease recurrence in 4 of 6 tumors tested. Consistent with the in vivo data, Notch1 inhibition reduces mammary tumorsphere forming activity in vitro. Using doxycycline-responsive tumor derived cell lines, we also identify the embryonic stem cell transcription factor Nanog as a novel Notch1-regulated gene in mammospheres. These data indicate that Notch1 contributes to mammary tumor initiating activity and raises the possibility that NOTCH therapeutics may have efficacy in human basal-like breast cancers associated with NOTCH activation.
2011-12-05 | GSE34146 | GEO
Project description:Most solid tumors seem to be organized in a hierarchy in which only a fraction of cells, termed tumor-initiating cells (TICs), is capable of disseminating new tumors after transplantation into recipient mice. However, whether a single TIC can induce a tumor or whether it requires additional TICs or non-TICs for tumor initiation is not known. Here we show that injections of single CD24+:Jag1- cells from Her2/Neu+ mammary tumors into recipient mammary glands induced tumors at a frequency of 1/22. Single cell-derived secondary tumors exhibited histology, flow cytometry and global expression profiles that were indistinguishable from primary tumors. Thus, a single TIC can act cell autonomously to induce a tumor and therefore complete eradication of all TICs would be required to cure cancer. Total RNA obtained from primary MMTV-Neu tumors, secondary tumors generated by lin- cell transplantation, and secondary tumors generated by a single TIC, were used for microarray analysis to determine differentially regulated genes in the secondary tumors. Cluster analysis based on gene expression were then performed to assess tumor similarity
2011-05-30 | E-GEOD-29616 | biostudies-arrayexpress
Project description:Therapeutic targeting MTDH-SND1 interaction Suppresses Breast Cancer Progression and Metastasis (GSE159764). To further elucidate the tumor intrinsic effects of the targeting and the adverse effects on normal mammary epithelial cells Mouse mammary tumor cells and normal mammary epithelial cells were isolated from transgenic mouse models and cultured in vitro 3D spheroids system. MMTV-PyMT tumor cells from cKO mouse in tumorsphere culture were treaed with tamoxifen to induce Mtdh KO, and compared to the mock treatment which maintain wild type Mtdh. Thus the tumor intrinsic effects can be determined Normal mammary epithelial cells were isolated from mouse mammary gland and cultured in vitro in mammosphere. The cells were treated with inhibitor C26A6 vs control and thus the adverse effects on normal MECs can be determined.
2021-09-07 | GSE174622 | GEO
Project description:Skin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development. The FACS sorted mammary stem cell (MaSC)/basal population from Pygo2 SSKO mammary gland displays biased differentiation towards luminal/alveolar lineage in vitro, and reduced regeneration rate of new mammary gland in vivo To gain the insight into gene expression profiles in control and Pygo2 SSKO mammary epithelial cells (MECs), we sorted the freshly isolated mouse MECs into MaSC/basal (Lin-CD29hiCD24+) and mature luminal population (Lin-CD29lowCD24+CD61-), and extract total RNA for cDNA microarray analysis
2013-09-05 | E-GEOD-45826 | biostudies-arrayexpress