Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload evoked by FBXL5 ablation gives rise to oxidative stress, tissue damage, inflammation and compensatory proliferation in hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting effect of FBXL5 deficiency in the liver is also operative in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis induced by iron overload. Dysregulation of FBXL5-mediated cellular iron homeostasis was also found to be associated with poor prognosis in human HCC, implicating FBXL5 plays a significant role in defense against hepatocarcinogenesis. Overall design: Total RNA was extracted from the nontumor and tumor tissue of an Alb-Cre/Fbxl5F/F male mouse (nontumor, n = 5; tumor, n = 5) or two littermate control Fbxl5F/F mice (nontumor, n = 6; tumor, n = 6) at 45 weeks of age.
Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
Specimen part, Cell line, Subject
View SamplesWe found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells.
Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.
Specimen part
View SamplesWe searched for roles of ZEB1 during EMT by RNA-seq in breast cancer cells. Overall design: Expression of mRNA in a basal type breast cancer cell line MDA-231-D transfected with ZEB1/ZEB2 siRNAs and stimulated with TGF-beta for 24 h.
ZEB1-regulated inflammatory phenotype in breast cancer cells.
Specimen part, Cell line, Subject
View SamplesAngiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part, Treatment
View SamplesAngiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sex, Specimen part
View SamplesAire in medullary thymic epithelial cells plays an essential role in the negative selection through expression of broad arrays of tissue-restricted antigens.
Ectopic Aire Expression in the Thymic Cortex Reveals Inherent Properties of Aire as a Tolerogenic Factor within the Medulla.
Specimen part, Disease
View SamplesEVI1 is one of the famous poor prognostic markers for a chemotherapy-resistant acute myeloid leukemia (AML). To identify molecular targets on the surface of leukemia cells with EVI1high expression, we compared the gene expression profiles of several AML cell lines by DNA microarray
CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression.
Cell line
View SamplesTumor microenvironment plays a pivotal role in cancer progression; however, little is known regarding how differences in the microenvironment affect characteristics of cancer cells. Here, we investigated the effects of tumor microenvironment on cancer cells by using mouse tumor models. After 3 cycles of inoculation and extraction of human pancreatic cancer cells, including SUIT-2 and Panc-1 cells, from tumors, distinct cancer cell lines were established; 3P cells from the pancreas obtained using the orthotopic tumor model, and 3sc cells from subcutaneous tissue obtained using the subcutaneous tumor model. On cell re-inoculation of these cells, the 3sc cells and, more prominently, the 3P cells, exhibited higher tumorigenic activity than the parental cells. The 3P cells specifically exhibited low E-cadherin expression and high invasiveness, suggesting that they were endowed with the highest malignant characteristics. RNA-sequence analysis demonstrated that distinct signaling pathways were activated in each cell line and that the 3P cells acquired a cancer stem cell-like phenotype. Among cancer stem cell-related genes, those specifically expressed in the 3P cells, including NES, may be potential new targets for cancer therapy. The mechanisms underlying the development of highly malignant cancer cell lines were investigated. Individual clones within the parental cells varied in tumor-forming ability, indicating the presence of cellular heterogeneity. Moreover, the gene expression profile of each clone changed after orthotopic inoculation. The present study thus suggests that both selection and education processes are involved in the development of highly malignant cancer cells. Overall design: Expression of mRNA in the highly malignant sublines of SUIT-2 and Panc-1 cells xenografted into mice.
Pancreatic tumor microenvironment confers highly malignant properties on pancreatic cancer cells.
Subject
View SamplesWe studied adipose tissue from wild type mice, kinin B1 receptor knockout mice (B1KO), and B1KO mice with rescued expression of kinin B1 receptor selectively in fat.
Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice.
Sex, Age, Specimen part
View SamplesUsing neutrophils from a cohort of normal individuals, we generated transcriptomic profile of 4 individuals. Overall design: Here we generated gene expression profile of neutrophil cells of 4 normal individuals.This data was integreated with DNA methylation profiles of same individuals.
Genome-wide DNA methylation map of human neutrophils reveals widespread inter-individual epigenetic variation.
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