Although the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a key cell cycle inhibitor. These experiments therefore shed a light on the context-specific role of STAT5a/b as tumor suppressors.
The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B negatively regulate cell proliferation through the activation of cyclin-dependent kinase inhibitor 2b (Cdkn2b) and Cdkn1a expression.
Specimen part
View SamplesRhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. Using a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub), which shows a regenerative phenotype, we sought to identify the underlying mechanism.
Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.
Specimen part, Treatment, Time
View SamplesIn this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.
Specimen part
View SamplesCancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Specimen part, Cell line
View SamplesWe used microarrays to evaluate the effect of SRPIN803 on gene expression in ARPE-19 cells.
Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice.
Cell line
View SamplesObjective: To determine the effects of age and topographic location on gene expression in human neural retina.
Effects of aging and anatomic location on gene expression in human retina.
Sex, Age
View SamplesDietary restriction regimens lead to enhanced stress resistance and extended lifespan in many species through the regulation of fasting and/or diet responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Several studies have implicated that the nervous system is involved in the regulation of longevity. However, it remains largely unknown whether the nervous system contributes to the regulation of lifespan and/or stress resistance elicited by fasting. In this study, we first investigated the role of the nervous system in fasting-elicited longevity and stress resistance. We found that lifespan extension in Caenorhabditis elegans caused by an intermittent fasting (IF) regimen was suppressed by functional defects in sensory neurons. The IF-induced longevity was also suppressed in a mutant that lacks the enzyme required for the synthesis of an amine neurotransmitter, octopamine (OA), which acts in the absence of food, i.e., under fasting conditions. Although OA administration did not significantly extend the lifespan, it enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.
Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans.
Specimen part
View SamplesIdiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP
Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis.
Specimen part, Disease, Disease stage
View SamplesAnalysis of spleen samples taken throughout the acute phase of infection from mice infected with virulent P. chabaudi CB strain
Transcriptome analysis of blood and spleen in virulent and avirulent mouse malaria infection.
Sex, Specimen part, Time
View SamplesRodent malaria parasite RNA hybridized on Illumina Mouse WG-6 v2.0 Expression BeadChip
Transcriptome analysis of blood and spleen in virulent and avirulent mouse malaria infection.
Sex, Specimen part
View Samples