Mus musculus
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ABSTRACT:
PROVIDER: PRJNA248457 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mutational and expression analyses of ER positive mammary tumors due to Prolactin ligand overexpression
| PRJNA489661 | ENA
Project description:Aged STAT1-/- female mice spontaneously develop ERa+ PR+ mammary tumors that exhibit strikingly similar hormone-sensitivity and -dependency as human ERa+ luminal breast cancers. We used microarray data to compare the genetic relationships between the STAT1-/- mammary tumors and human breast cancers. We compared five STAT1-/- mammary tumor datasets with the publicaly available datasets of human breast cancers and those from other mouse mammary tumor models.
2011-12-15 | E-GEOD-31942 | biostudies-arrayexpress
Project description:Aged STAT1-/- female mice spontaneously develop ERa+ PR+ mammary tumors that exhibit strikingly similar hormone-sensitivity and -dependency as human ERa+ luminal breast cancers. We used microarray data to compare the genetic relationships between the STAT1-/- mammary tumors and human breast cancers.
2011-12-15 | GSE31942 | GEO
Project description:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favourable patient prognosis, which is in part, attributed to the Estrogen Receptor-alpha (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favourable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer. FOXA1 siRNA treated breast cell lines compared directly to nonspecific siRNA treated cell lines using Agilent 4X44 microarrays.
2012-03-09 | E-GEOD-31003 | biostudies-arrayexpress
Project description:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favorable patient prognosis, which is in part, attributed to the Estrogen Receptor-α (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favorable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer.
2012-03-09 | GSE31003 | GEO
Project description:RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss.
2014-11-26 | GSE47375 | GEO
Project description:RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss. Thoracic and inguinal mammary glands from 3 MMTV-Cre;Runx1L/L;R26Y and 3 MMTV-Cre;Runx1+/+;R26Y adult virgin females were dissected out, minced and digested to single cell suspension. Runx1L is the floxed conditional knockout allele of Runx1. R26Y is a conditional YFP reporter that would be turned on upon Cre-mediated recombination. FACSaria machine was used to sort out the YFP-marked luminal epithelial cell population of each of these 6 mice. Total RNA was isolated with Qiagen RNeasy kit and subsequently amplified by Nugen V2 and applied to Affymetrix mouse genome 430 2.0 arrays.
2014-11-26 | E-GEOD-47375 | biostudies-arrayexpress
Project description:Recent analyses have identified heterogeneity in estrogen receptor (ER)-positive breast cancer. There are so-called luminal A and luminal B subtypes, and the characteristics, such as response to endocrine therapy and chemotherapy and prognosis, are different in these two subtypes of breast cancer. In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissues were compared between highly and incompletely endocrine responsive tumors by miRNA and mRNA microarrays. Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs in these two groups. We identified one miRNA that was downregulated in highly endocrine responsive tumors and 8 miRNAs that were downregulated in incompletely endocrine responsive tumors, and target genes of these miRNAs were predicted using TargetScan and MiRanda. Protein expression patterns of the predicted target genes and the genes that were identified by mRNA expression profiling were analyzed in ER-positive breast cancer samples by immunohistochemistry. We identified a novel protein that might be associated with characteristics of ER-positive breast cancer.
2013-03-04 | GSE38279 | GEO
Project description:Recent analyses have identified heterogeneity in estrogen receptor (ER)-positive breast cancer. There are so-called luminal A and luminal B subtypes, and the characteristics, such as response to endocrine therapy and chemotherapy and prognosis, are different in these two subtypes of breast cancer. In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissues were compared between highly and incompletely endocrine responsive tumors by miRNA and mRNA microarrays. Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs in these two groups. We identified one miRNA that was downregulated in highly endocrine responsive tumors and 8 miRNAs that were downregulated in incompletely endocrine responsive tumors, and target genes of these miRNAs were predicted using TargetScan and MiRanda. Protein expression patterns of the predicted target genes and the genes that were identified by mRNA expression profiling were analyzed in ER-positive breast cancer samples by immunohistochemistry. We identified a novel protein that might be associated with characteristics of ER-positive breast cancer.
2013-03-04 | GSE38278 | 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 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