This SuperSeries is composed of the SubSeries listed below.
Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.
Sex, Age, Specimen part, Treatment
View SamplesProgesterone (P) acting through its cognate nuclear receptors (PRs) plays an essential role in driving pregnancy-associated branching morphogenesis of the mammary gland. However, the fundamental mechanisms, including global cistromic and acute genomic transcriptional responses that are required to elicit active branching morphogenesis in response to P, have not been elucidated. We used microarray analysis to identify global gene expression signatures that are acutely regulated by PRs in the mouse mammary gland after acute P treatment.
Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesThe cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesStem cell antigen-1 (Sca-1 or Ly6A) is a member of the Ly6 family of glycosyl phostidylinositol (GPI)-anchored cell surface proteins. To determine the potential mechanisms by which Sca-1 regulates cell migration, adhesion, and tumor development; we performed an Affymetrix mouse genome 430A 2.0 array on cDNA comparing shLuc and shSca-1 from cells grown in vitro.
Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration.
Specimen part, Cell line
View SamplesmiR-34c inhibits Dicer/Pten double knockout mouse serous epithelial cancer cell proliferation by inducing cell cycle arrest and apoptosis. We found that miR-34c had a more dramatic effect on inhibiting tumor cell viability than let-7b. The action of miR-34c induced tumor cell cycle arrest in G1 phase and apoptosis and was accompanied with the regulation of key genes involved in cell proliferation and cell cycle G1/S transition. miR-34c suppressed the expression of EZH2 and MYBL2, which may transcriptionally and functionally activate CDKN1C.
Functional analysis of miR-34c as a putative tumor suppressor in high-grade serous ovarian cancer.
Cell line
View SamplesThe cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesUterine double conditional inactivation of Smad2 and Smad3 in mice results in endometrial dysregulation, infertility, and uterine cancer. Smad2/3 cKO mice demonstrate abnormal expression of genes involved in inflammation, cell-cycle checkpoint, migration, steroid biosynthesis, and SMAD1/5-driven genes. We performed RNA-sequencing to identify the gene expression differences between the uterine epithelium of control and Smad2/3 cKO. To control for estrous cycle variations, the uterine epithelium was collected from mice at 0.5 dpc. Global gene expression profiles of Smad2/3 cKO versus control mice was analyzed. Our RNA sequencing analysis was performed at 6 weeks of life and already showed significant differences in migratory (Agr2,Slit2) and inflammatory (Ccl20, Crispld2) markers between Smad2/3 cKO and control mice. Overall design: Two group comparison: uterine epithelium of control and Smad2/3 cKO mice. We generated a conditional knockout of Smad2/3 in the uterus and demonstrated that Smad2/3 plays a critical role in the endometrium, with disruption resulting in pubertal-onset uterine hyperplasia and ultimately fatal uterine cancer.
Uterine double-conditional inactivation of <i>Smad2</i> and <i>Smad3</i> in mice causes endometrial dysregulation, infertility, and uterine cancer.
Specimen part, Subject
View SamplesProfiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2).
Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors.
Cell line
View SamplesMyotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes.
The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.
Specimen part, Time
View Samples