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Microarray expression profiling of Runx1-null and wildtype mouse mammary epithelial cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE47377 | GEO | 2014/11/26

SECONDARY ACCESSION(S): PRJNA205360

REPOSITORIES: GEO

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Microarray expression profiling of Runx1-null and wildtype mouse mammary epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-11-26 | E-GEOD-47377 | biostudies-arrayexpress

Microarray expression profiling of Runx1-null and wildtype mouse mammary epithelial cells

Project description:Microarray expression profiling of Runx1-null and wildtype mouse mammary epithelial cells

| PRJNA205360 | ENA

Microarray expression profiling study of Runx1-null and wild type luminal mammary epithelial cells

2014-11-26 | GSE47375 | GEO

Microarray expression profiling study of Runx1-null and wild type luminal mammary epithelial cells

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

Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition.

Project description:Runx1 is a well characterized transcription factor essential for hematopoietic differentiation and Runx1 mutations are the cause of leukemias. Runx1 is highly expressed in normal epithelium of most glands and recently has been associated with solid tumors. Notably, the function of Runx1 in the mammary gland and how it is involved in initiation and progression of breast cancer is still unclear. Here we demonstrate the consequences of Runx1 loss in normal mammary epithelial and breast cancer cells. We first observed that Runx1 is decreased in tumorigenic and metastatic breast cancer cells. We also observed loss of Runx1 expression upon induction of epithelial-mesenchymal transition (EMT) in MCF10A (normal-like) cells. Furthermore depletion of Runx1 in MCF10A cells resulted in striking changes in cell shape, leading to mesenchymal cell morphology. The epithelial phenotype could be restored in breast cancer cells by re-expressing Runx1. Analyses of breast tumors and patient data revealed that low Runx1 expression is associated with poor prognosis and decreased survival. We addressed mechanisms for the function of Runx1 in maintaining the epithelial phenotype and find Runx1 directly regulates E-cadherin; and serves as a downstream transcription factor mediating TGFβ signaling. We also observed through global gene expression profiling of growth factor depleted cells that induction of EMT and loss of Runx1 is associated with activation of TGFβ and WNT pathways. Thus these findings have identified a novel function for Runx1 in sustaining normal epithelial morphology and preventing EMT and suggest Runx1 levels could be a prognostic indicator of tumor progression.

| S-EPMC5392273 | biostudies-literature

Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells.

Project description:BackgroundThe small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGF? signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type.ResultsWe report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGF? signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR).ConclusionsOur findings suggest activation of the ISR may be a common mechanism underlying HF biological effects.

| S-EPMC3197508 | biostudies-literature

microRNA expression profiles of distinct human and mouse mammary epithelial cell types

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-20 | E-GEOD-67056 | biostudies-arrayexpress

scATAC-seq and scRNA-seq of Mouse Mammary Epithelial Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-09-14 | GSE157890 | GEO

PDEF knockdown and overexpression in mammary epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-03-29 | E-GEOD-40987 | biostudies-arrayexpress

Microarray expression profiling of distinct subsets of mouse mammary epithelial cells

Project description:The purpose of this microarray experiment was to obtain reference gene expression patterns of a number of epithelial cell populations [mammary stem cells (MASC), luminal progenitors (LP), alveolar luminal stem/progenitor cells (WC virgin-these are mammary epithelial cells genetically marked by Wap-Cre in virgin females), mature luminal cells (ML, mainly represent ductal luminal cells in virgin females), and alveolar luminal cells (WC preg – these are alveolar cells genetically marked by Wap-Cre during mid-gestation)] present in the mammary gland of wildtype adult mice on a C57BL6 genetic background.

2014-11-26 | GSE47376 | GEO

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