We sought to elucidate the molecular mechanisms whereby LIN28B functions by comparing the gene expression profile of cells constitutively expressing LIN28B to empty vector controls.
LIN28B promotes colon cancer progression and metastasis.
Disease, Cell line
View SamplesTo begin to identify genes involved in the transdifferentiation process we analyzed Barretts esophagus (with no dysplasia), normal esophagus and small intestine biopsy samples by Affymetrix microarray.
Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett's esophagus.
No sample metadata fields
View SamplesParvin-beta is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-beta contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-beta expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-beta was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Gene expression profiles of vector control and Parvin-beta transfected MDA-MB-231 cells cultured on (A) monomeric type I collagen coated plastic, (B) embedded in a type I collagen gel, and (C) embedded in basement membrane (growth factor reduced Matrigel), were compared. Interestingly, Parvin-beta re-expression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARgamma) and a concomitant increase in lipogenic gene expression as a downstream effector of PPARgamma. Importantly, Parvin-beta suppressed breast cancer growth in vivo with associated decreased proliferation. These data suggest that Parvin-beta might influence breast cancer progression..
Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.
No sample metadata fields
View SamplesBackground & Aims: Perturbations in pancreatic ductal bicarbonate secretion often result in chronic pancreatitis. Although the physiological mechanism of ductal secretion is known, its transcriptional control is not well characterized. Here, we investigate the role of the transcription factor Hematopoietically-expressed homeobox protein (Hhex) in pancreatic secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histological and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells (PDCs) were isolated to discover differentially expressed transcripts upon acute Hhex ablation. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia did not result from perturbations in primary cilia, but was consistent with the effects of primary ductal hypertension. RNA-seq analysis of Hhex-ablated PDCs indicated the G-protein coupled receptor Natriuretic peptide receptor 3, implicated in paracrine signaling, was upregulated 4.70-fold. Conclusions: Although Hhex is dispensable for adult pancreatic function, ablation of Hhex in pancreatic progenitors results in profound pancreatitis that is consistent with primary ductal hypertension. Our data highlight the critical role of paracrine signaling in maintaining ductal homeostasis, especially in early life, and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Overall design: Pancreatic primary ductal cells (PDCs) were isolated from uninduced adult HhexL/L;Sox9CreERT2 (n=2) and littermate control HhexL/L (n=2) mice. PDCs were treated with 500nM 4-hydroxytamoxifen in vitro for 4 days, and then RNA was collected for transcriptome analysis.
Spontaneous Pancreatitis Caused by Tissue-Specific Gene Ablation of <i>Hhex</i> in Mice.
No sample metadata fields
View SamplesWe identified spatially restricted transcription factors and found SOX15 expression confined to stratified esophageal epithelium, with attenuation in Barrett''s esophagus. SOX15 binds esophagus-specific loci and its loss in human esophageal cells affected esophagus-specific transcripts Overall design: [RNA-Seq] Total RNA isolated from CPA control cells and CPA cells following SOX15 depletion, samples were prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75 base pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype. [ChIP-Seq] Examine SOX15-chromatin binding in CPA cells.
SOX15 governs transcription in human stratified epithelia and a subset of esophageal adenocarcinomas.
No sample metadata fields
View SamplesTelomeres shorten with each round of cell division, and the expression of telomerase serves to lengthen telomeres. In the absence of telomerase, telomeres shorten to the point of uncapping and causes defects in tissues with high turnover, including the intestinal epithelium. In mice lacking telomerase (e.g. mTR-/-), telomeres critically shorten after several generations of telomerase deficiency, with pronounced defects in their intestine.
Mutual reinforcement between telomere capping and canonical Wnt signalling in the intestinal stem cell niche.
Specimen part
View SamplesCdx2/IL-1beta mice have less intestinal metaplasia at the squamocolumnar junction thanIL-1beta mice alone.
Immature myeloid progenitors promote disease progression in a mouse model of Barrett's-like metaplasia.
No sample metadata fields
View SamplesTo determine the molecular basis of gene regulation in pancreatic ductal epithelial cells, we developed methods for the isolation of this cell population during mouse development and normal adult homeostasis, as well as in conditions with ductal features (acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC)). Our technique utilizes the specificity of Dolichos biflorus Agglutinin (DBA) lectin marking the entire normal ductal tree, including terminal intercalated ducts (putative sites of stem or progenitor cells) and ductal structures in ADM and PanIN. We used ferromagnetic-labeled DBA lectin to isolate ductal structures. Ductal cells were isolated under the following conditions: (1) Embryonic Development in wild type mice: E14.5, E15.5, E16.5, and postnatal day 1 (P1); (2) Injury and regeneration (pancreatitis) 0, 1, 3, 5 days following cerulein-induced acute pancreatitis. Cerulein is a cholecystokinin analog which produces a self-limited pancreatitis with injury and subsequent regeneration and repair, completed five days after insult; and (3) Pdx1-Cre;LSL-KrasG12D/+ mice aged 10 and 20 weeks that harbor PanIN lesions and a subset develop PDAC. Ductal/PanIN cells were isolated from these mice and appropriate control mice (Pdx1-Cre;Kras+/+).
The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis.
Age, Specimen part, Treatment, Time
View SamplesLoss of p120ctn results in dysplasia and invasive cancer in the mouse esophagus and squamous forestomach.
Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene.
Specimen part
View SamplesThe estrogen-dependence of breast cancer has long been recognized, however, the role of 17-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that
Epithelial to mesenchymal transition in human breast epithelial cells transformed by 17beta-estradiol.
No sample metadata fields
View Samples