Endocrine therapy is the main therapeutic option for patients with estrogen receptor alpha positive (ER+) breast cancer. Nevertheless, most of them become estrogen-independent and relapse after the treatment. Ret is a tyrosine kinase receptor that shows elevated expression levels in ER+ human breast tumors. In this study, we demonstrate that activation of the Ret receptor promotes proliferation as well as cell migration irrespective of endocrine therapy. Microarray data show that Ret activation involves changes in the expression of inflammatory- and motility-related genes. In vivo treatment with a Ret pathway inhibitor in a ER+/Ret+ mouse mammary cancer model, reduces tumor growth and lung metastasis even after endocrine therapy. Additionally, we show a connection between Ret and inflammatory pathways. The pro-inflamatory cytokine IL6 lies at the core of this regulation, which involves a positive feedback loop with IL6 and the Ret pathway reciprocally stimulating each other to further leading metastasis risk. Our findings provide insight into endocrine resistance mechanism and point at the Ret pathway as a potential target for future therapies.
Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells.
Cell line, Treatment, Time
View SamplesPost-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Overall design: Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)
Using Next-Generation Sequencing Transcriptomics To Determine Markers of Post-traumatic Symptoms: Preliminary Findings from a Post-deployment Cohort of Soldiers.
Sex, Subject
View SamplesM cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius, Eschericha coli and Bacteroides fragilis, on M cell gene expression.
Differential intestinal M-cell gene expression response to gut commensals.
Specimen part, Treatment
View SamplesAnalysis of the regulation of gene expression profiles by retinoblastoma-1 in Sertoli cells. Conditional knockout of Rb1 in Sertoli cells led to progressive infertiliy in male mice that occured between 10 and 14 weeks of age. Results of gene expression studies performed on 6 week-old purified Sertoli cells helped elucidate the key role of RB1 in mature, differentiated Sertoli cells.
Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part, Treatment
View SamplesUlipristal acetate (UPA), also referred to as VA/CDB-2914, is a new and promising emergency contraceptive. It is a selective progesterone receptor modulator (SPRM) that has been approved in Europe and the USA for emergency contraception.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part, Treatment
View SamplesPrevious studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part
View SamplesExperimental Design
Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach.
No sample metadata fields
View SamplesThis study describes a temporal profile of gene expression from normal human fetal testes and ovaries. Gonads from 34 fetuses between 9 weeks and 20 weeks of gestation were obtained from the Department of Pathology and the Birth Defects Research Laboratory at the University of Washington. Relative transcript levels were determined using the Affymetrix Human Genome U133A Plus 2.0 arrays.
Global gene expression in the human fetal testis and ovary.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity.
Specimen part
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