Our previous study using nude rats revealed that the parental JDCaP xenografts predominantly expressed full-length androgen receptor (AR) whereas the relapsed JDCaP xenografts after castration acquired AR splice variants including AR-V7 and ARv567es. To understand molecular mechanisms underlying the acquisition of AR splice variants in the JDCaP model, we performed microarray analysis using RNA samples of the xenografts without castration (Parent), the relapsed xenografts overexpressing full-length AR and AR-V7 (ARhiV7hi), and the relapsed xenografts expressing ARv567es (ARv567es).
The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.
Specimen part
View SamplesGlobal DNA hypomethylation and DNA hypermethylation of promoter regionsincluding tumor suppressor genesare frequently detected in human cancers. Although many studies have suggested a contribution to carcinogenesis, it is still unclear whether the aberrant DNA hypomethylation observed in tumors is a consequence or a cause of cancer. We found that overexpression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA hypomethylation and transformation in NIH3T3 cells. This hypomethylation was due to the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent impairment of Dnmt1 localization. In addition, enforced expression of Stella enhanced the metastatic ability of B16 melanoma cells through the induction of metastasis-related genes by inducing DNA hypomethylation of their promoter regions. Such DNA hypomethylation itself causes cellular transformation and metastatic ability. These data provide new insight into the function of global DNA hypomethylation in carcinogenesis.
Global DNA hypomethylation coupled to cellular transformation and metastatic ability.
Cell line
View SamplesAtrial specific knockout of Nkx2-5 results in hyperplastic atria with ASD and conduction defects. To examine how Nkx2-5 regulates cardiac proliferation at late gestational stages, RNA-seq was performed. Overall design: Examination of expression profile of 2 Nkx2-5-null atria and 3 controls
Nkx2-5 suppresses the proliferation of atrial myocytes and conduction system.
No sample metadata fields
View SamplesPoorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cells. Although accumulating evidence from clinicopathological studies suggests a strong association between this variant of synovial sarcoma and poor prognosis, little has been reported on the molecular basis of PDSS. To gain insight into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlated highly with histological subtype, namely, monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion, and up-regulation of genes on a specific chromosomal locus, 8q21.11. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase (RT)-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct genetic group based on expression profiles.
Gene expression profiling of synovial sarcoma: distinct signature of poorly differentiated type.
Sex, Specimen part
View SamplesTo determine the role of NOTCH3 in human esophageal epitheila homeostasis/squamous cell differentiation
A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors.
Specimen part, Treatment
View SamplesTenascin-C (TNC), a cancer-associated extracellular matrix glycoprotein, plays a pivotal role in tumor growth. To identify the genes regulated by TNC during tumor growth, we performed a tumor growth assay, DNA microarray analysis, and quantitative real-time PCR (qRT-PCR). Mouse mammary tumor cells were subcutaneously inoculated into GRS/A (WT) and GRS/A-TgH(Tnc) (TNKO) mice. Tumors in WT mice significantly increased in volume with expressing TNC while tumors in TNKO mice showed hardly detectable levels of TNC. Tumor gene expression profiles between TNKO and WT mice were compared using DNA microarray analysis. We found that 447 genes were up-regulated (TNKO>WT) and 667 genes were down-regulated (TNKO<WT) in the TNKO group. We then classified these genes by Gene Ontology (GO) terms in order to elucidate their biological function. There were three GO terms found related to tumor growth, namely, acute inflammatory response, cell adhesion, and response to wounding. Eighty-three of the genes primarily involved in these GO terms were further validated by qRT-PCR. Eight genes: Tnc, Cxcl2, Cxcl1, Hbegf, Chl1, Cd44, Serpina3n, and F3 were significantly down-regulated relative to the WT. Eighteen genes: Saa3, P2rx7, Ptgs1, Ptger2, Comp, Steap4, Il1rn, Il1b, Ncf1, Mst1, Nfb1, Ctsb, Tnfrsf1a, Tnfrsf1b, Cd24a, Adam17, Mtpn, and Sox4 were significantly up-regulated relative to the WT. These results support our hypothesis that TNC has multi-faceted effects on both the tumor cells and their microenvironment. First, TNC acts on the tumor cells directly by up-regulating genes involved in cancer cell proliferation through the CXCL1/2 and CXCR2 pathway. Second, TNC controls the tumor microenvironment by promoting angiogenesis through the CXCL1/2 and CXCR2 pathway, and by suppressing inflammatory gene expression through a separate pathway.
Comprehensive DNA microarray expression profiles of tumors in tenascin-C-knockout mice.
Sex, Specimen part
View SamplesHematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here, we examined the hemogenic activity of the developing endocardium. Mouse heart explants generated myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arose from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and was transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, were expressed in and required for the hemogenic activity of the endocardium. Together, these data suggest that a subset of endocardial and yolk sac endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors.
Haemogenic endocardium contributes to transient definitive haematopoiesis.
Specimen part
View SamplesExpression profile of embryonic retinas expressing exogenous c-hairy1, Delta-1, or Wnt2b. These genes inhibits neuronal differentiation, and the results provide insight into the mechanism that keeps retinal progenitor cells undifferentiated.
Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell-like progenitor cells in the chick ciliary marginal zone.
Specimen part
View SamplesWe report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.
Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency.
No sample metadata fields
View SamplesNCCs and NCC-derived MSCs were induced from FOP-iPSCs and control iPSCs, and their expresion profiles were compared.
Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.
Specimen part
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