Characterization of human breast cancer xenografts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE28570 | GEO | 2011/07/07
SECONDARY ACCESSION(S): PRJNA139023
REPOSITORIES: GEO
Similar Datasets
Project description:A bank of human breast tumor xenografts was established by serial passage of primary breast tumor fragments in the cleared mammary fat pads of immuno-compromised NOD-SCID-IL2Rgammac–/– mice. The 15 expression profiles from five different tumors were classified using the ClaNC method [1]. The training data set consisted of 94 samples from Herschkowitz et al. [2]; class labels were based on tumor subtype (Basal-like, Luminal A, Luminal B, Claudin-low, HER2+/ER- and Normal breast-like). [1] Dabney AR (2005) Classification of microarrays to nearest centroids. Bioinformatics 21:4148-4154. [2] Herschkowitz JI, et al. (2007) Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8:R76. Total RNA obtained from xenograft tumors from 5 different patients have been profiled in triplicate on the Illumina HT-12 BeadChip platform.
2011-07-07 | E-GEOD-28570 | biostudies-arrayexpress
Project description:A bank of human breast tumor xenografts was established by serial passage of primary breast tumor fragments in the cleared mammary fat pads of immuno-compromised NOD-SCID-IL2Rgammac-/- mice. The expression profiles from four different tumors (23T, 315T, 50T and 838T) were classified using diagonal discriminant analysis. The training data set consisted of 1992 samples from Curtis et al. (2012, PMID: 22522925); class labels were based on tumor subtype information provided (Basal-like, Luminal A, Luminal B, HER2-enriched and Normal breast-like).
2013-06-09 | GSE47369 | GEO
Project description:A bank of human breast tumor xenografts was established by serial passage of primary breast tumor fragments in the cleared mammary fat pads of immuno-compromised NOD-SCID-IL2Rgammac-/- mice. The expression profiles from four different tumors (23T, 315T, 50T and 838T) were classified using diagonal discriminant analysis. The training data set consisted of 1992 samples from Curtis et al. (2012, PMID: 22522925); class labels were based on tumor subtype information provided (Basal-like, Luminal A, Luminal B, HER2-enriched and Normal breast-like). Total RNA obtained from xenograft tumors from different patients have been profiled on the Illumina HT-12 BeadChip platform.
2013-06-09 | E-GEOD-47369 | biostudies-arrayexpress
Project description:We are generating a new mouse model for breast cancer heterogenaity using lentiviral infection to integrate the sporatically transforming EF1α-PyMT10C or Muc-PyMT10C lentivirus into mouse mammary epithelial cell genomes. We then transplant those cells into cleared mammary fat pads of recipient mice, allowing tumors to develop from luminal , myoepithelial, stem and progenitor cell lineages. We developed a wide variety of tumors including rare histologies such as squamous, tubular, spindloid and lipid rich. We used microarray analysis to compare our mouse model with a microarray analysis of 9 established mouse models (Herschkowitz, J.I. et al. Genome Biology, 2007). Heirarchal clustering was used to establish the molecular subtype of tumors developed through the lentiviral-PyMT mouse model. In addition, micrarray analysis was used in conjunction with GeneSifter and GO ontology to identify unique pathways for each of the rare tumor types.
2012-08-10 | GSE40001 | GEO
Project description:One of the greatest advances in therapy of estrogen receptor positive breast cancer has been the development of endocrine therapy. More than two thirds of primary breast tumors express estrogen receptor alpha (ERα) and their growth is mainly dependent on estrogen receptor activity. Several therapeutic approaches have thus been designed to inhibit ER activity in breast tissue. Tamoxifen, a selective ER modulator, is one of the main treatment options for premenopausal women with advanced ER positive breast cancer, and has also become well established as adjuvant therapy in the early breast cancer setting (Davies et al., 2011; Group, 1998; Jaiyesimi et al., 1995). In contrast to tamoxifen, which in other tissues such as bone and endometrium, can exert partial agonistic activity (Braithwaite et al., 2003; Fisher et al., 1994; Pietras, 2006), the selective ER downregulator, fulvestrant, is a potent ER antagonist. Binding of fulvestrant to ER inhibits receptor dimerization and nuclear uptake, prevents estrogen-response element binding and accelerates ER degradation (Dauvois et al., 1993; Dowsett et al., 2005; Fawell et al., 1990; Wakeling et al., 1991). Fulvestrant is approved for treatment of postmenopausal women with advanced breast cancer who have relapsed or progressed on first-line endocrine therapy (Howell et al., 2002; Osborne et al., 2002; Robertson et al., 2003). Estrogen deprivation by treatment with aromatase inhibitors (such as letrozole, anastrozole or exemestane) which block synthesis of estrogens is another effective therapy option in postmenopausal women (Bonneterre et al., 2000; Cuzick et al., 2010; Dowsett et al., 2010; Mouridsen et al., 2001; Nabholtz et al., 2000). The large majority of patients with ER+ breast cancer experience an initial response to endocrine therapy, however, in many of these patients, the disease subsequently progresses and eventually anti-estrogen therapy ceases to have effect. Biomarkers predicting response to estrogen deprivation and new alternative treatments targeting the pathways supporting estrogen independent growth are therefore urgently needed (Patani and Martin, 2014; Patani et al., 2013). In order to understand how tumors respond to withdrawal of their main growth signal, a comparison of molecular features of tumor before and during endocrine therapy is necessary, and the fate of individual cancer cell sub-clones should be monitored. Since studies of cellular dynamics are very difficult to perform with clinical material, we made use of a patient derived, estrogen dependent, orthotopically growing luminal-like primary breast cancer xenograft model (PDX) (Bergamaschi et al., 2009; Huuse et al., 2012). This PDX model is a representative model for luminal breast cancers as the molecular characteristics, cellular heterogeneity and estrogen dependency of the primary tumor are retained over many passages. Functionally different subpopulations of cancer cells were previously defined by expression of the markers CD24 and SSEA-4 in this model (Skrbo et al., 2014), and it is therefore a suitable model for comparison of cellular and molecular effects of estrogen deprivation and ER-signaling inhibition. In this study, a quantitative MS-based proteomic analysis using SILAC and a label-free approach were performed, aiming to map changes in protein expression induced by endocrine therapy. Inhibition of ER-signaling seemed to induce CD24 and SSEA-4 expression on residual tumor cells. Proteomic analysis revealed overexpression of enzymes involved in TCA cycle, oxidative phosphorylation and fatty acid beta-oxidation following endocrine treatment when compared to untreated tumors. These results indicated possible reprogramming of cell metabolism and utilization of aerobic respiration, i.e. oxidative phosphorylation, in response to endocrine therapy.
2022-02-28 | PXD002352 | Pride
Project description:Generating a new mouse model for breast cancer heterogenaity. We use lentiviral infection to integrate the sporatically transforming EF1α-PyMT10C or Muc-PyMT10C into mouse mammary epithelial cell genomes. We then transplant those cells into cleared mammary fat pads of recipient mice, allowing tumors to develop from luminal , myoepithelial, stem and progenitor cell lineages. We developed a wide variety of tumors including rare histologies such as squamous, tubular, spindloid and lipid rich. We used microarray analysis to compare our mouse model with a microarray analysis of 9 established mouse models (Herschkowitz, J.I. et al. Genome Biology, 2007). Heirarchal clustering was used to establish the molecular subtype of tumors developed through the lentiviral-PyMT mouse model. In addition, micrarray analysis was used in conjunction with GeneSifter and GO ontology to identify unique pathways for each of the rare tumor types 43 total microarrays were generated from lentiviral-PyMT tumors, MMTV-PyMT transgenic tumors, and embryonic samples . Nine samples were two color arrays run at UNC microarray facility, while 34 were one color arrays run at Huntsman Cancer Instutite. The two color arrays were treated as one color arrays, we used the Cy3 intensity data for analysis. These data were merged and normalized (quantile and combat) with previously published arrays from UNC. Data were filtered on an intrinsic gene set developed in 2007 (Herschkowitz, J.I. et al. Genome Biology, 2007) and clustered using euclidian distance metrics This GEO submission consists of the 34 one color arrays run at Huntsman Cancer Instutite. The nine two color arrays run at UNC microarray facility are not included.
2012-08-09 | E-GEOD-40001 | biostudies-arrayexpress
Project description:The transcription factor c-Myb has been well characterized as an oncogene in several human tumor types, and its expression in the hematopoietic stem/progenitor cell population is essential for proper hematopoiesis. However, the role of c-Myb in mammopoeisis and breast tumorigenesis is poorly understood, despite its high expression in the majority of breast cancer cases (60-80%). We find that c-Myb high expression in human breast tumors correlates with the luminal/ER+ phenotype and a good prognosis. RNAi knock-down of endogenous c-Myb levels in the MCF7 luminal breast tumor cell line increases tumorigenesis both in vitro and in vivo, suggesting a tumor suppressor role in luminal breast cancer. We created a mammary-derived c-Myb expression signature and found it to be highly correlated with a published mature luminal mammary cell signature and least correlated with a mammary stem/progenitor lineage gene signature. These data describe, for the first time, a tumor suppressor role for the c-Myb proto-oncogene in breast cancer that has implications for understanding luminal tumorigenesis and for guiding treatment. refXsample
2010-10-15 | E-GEOD-21371 | biostudies-arrayexpress
Project description:Age and physiological status like menopause are key factors in mammary development and are associated with breast cancer risk. Less clear is what factors influence breast cancer intrinsic subtypes that are associated with prognosis. Here, we investigated the age of the host in a mammary chimera model. The mammary glands of wildtype BALB/c mice were cleared of endogenous epithelium at 3 weeks of age and subsequently transplanted during puberty (5 weeks) or upon maturation (10 weeks) with syngeneic Trp53null mammary fragments. The Trp53null mammary epithelium undergoes a high rate of neoplastic transformation, such that carcinomas arise over the course of a year. Tumors arose more rapidly (p=0.003, log-rank test) when transplanted to adult hosts (AH, n=89) compared to tumors arising following transplantation into juvenile hosts (JH, n=55). However, JH tumors grew several times faster than AH tumors, were more perfused as indicated by 2-fold larger blood vessels (p=0.015), and exhibited a 2-fold higher mitotic index (p=0.009). Transplantation into juvenile hosts (JH) gave rise to 80% ER positive tumors compared to 60% in adult hosts. However, tumor cells were significantly more ER immunoreactive (p=0.0001) in JH tumors compared to those in AH tumors and were more highly positive for insulin like growth factor receptor phosphorylation (p=0.026). Expression profiles of JH (n=15) and AH (n=12) tumors identified 243 differentially expressed genes. The main biological processes enriched in JH tumors were organ morphology, proliferation, and lipid metabolism. An expression profile of juvenile versus adult (JVA) tumors revealed a luminal transcriptional program, characterized by expression of Foxa1, Igf2, Ccnd1 and Fgfr2. The human homologs of JVA genes (JVAh) were used to create two centroids (AHh or JHh) to classify human breast cancers from archival microarray datasets in two-dimensional space. Luminal human breast cancers were more like JH tumors compared to basal-like cancers, whereas luminal A tumors were more like JH tumors than luminal B tumors. Consistent with this, JVAh genes segregated human luminal A from luminal B breast cancers via hierarchical clustering. The distinct biology of tumors arising from tissue undergoing morphogenesis in the context of puberty suggests that young age at neoplastic transformation promotes a luminal tumor phenotype and supports the contention that the tumor intrinsic subtype is influenced by physiological status at the time of putative initiation.
2014-12-01 | GSE56726 | GEO
Project description:The goal of the experiment was to carry out a transcriptome analysis of the three main epithelial cell populations of the mouse mammary gland, the basal/myoepithelial, luminal estrogen receptor negative (ER-) and luminal estrogen receptor positive (ER+) cells, to identify cell-type specific differences in gene expression. Three replicates arrays were carried out for each of the three populations (a total of nine arrays). Each replicate was a genuine biological replicate from RNA harvested from completely independent cell preparations. Each sample was isolated from preparations of mammary epithelium derived fourth mammary fat pads of 8 * 10 week old virgin female FVB mice. Each preparation was from a pool of 10 * 20 animals (20 * 40 fat pads).
2009-04-20 | E-TABM-683 | biostudies-arrayexpress
Project description:To investigate the impact of combined Rb and p53 loss in mammary tumorigenesis, we used transgenic and viral approaches to delete Rb and p53 floxed alleles specifically in the mouse mammary epithelium. Although MMTV-Cre (NLST) targets stem/bi-potent progenitors in the mammary gland, a subset of MMTV-Cre:Rbf/f;p53f/f mice developed non-mammary tumors. Thus, freshly isolated primary mammary epithelial cells from these animals were transplanted into the mammary fat pads of immunodeficient mice and monitored for tumor formation. In addition, primary MECs were isolated from Cre-negative Rbf/f;p53f/f mice, infected with Ad-Cre followed by orthotopic transplantation. In all these cases, resulting tumors shared similar spindle-shape histology, expressed high levels of vimentin, a mesenchymal marker, but not E-cadherin, a luminal marker, and were classified as adeno-sacrcomatoid/spindle-cell/mesenchymal-like breast cancer. We used microarrays to detect differentially expressed genes in the Rb/p53 double-knock-out vs p53 single deletion or normal mammary tissue. Total RNA was extracted from tumors developed by double Trizol method and hybridized on Affymetrix microarrays
2014-10-03 | E-GEOD-62016 | biostudies-arrayexpress