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 SamplesMerm1/Wbscr22 is one of genes in chromosomal region deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Wbscr22 contains a nuclear localization signal and an S-adenosyl-L-methionine-dependent methyltransferase fold, but its real function is completely unknown.In this study, to examine the function, we compared the gene expression profiles between control and Merm1/Wbscr22 knock-downed tumor cells.
The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis.
Cell line, Treatment
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 SamplesGenistein is one of the flabonoids which is included in high concentration in soy and has a high estrogenic activity. Beneficial effects of estrogen or hormone replacement therapy (HRT) on muscle mass or muscle atrophy have been demonstrated. We investigated the preventive effects and underlying mechanisms of genistein intake on denervation-induced muscle atrophy.
Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α.
Sex, Age, Specimen part, Treatment
View SamplesPurpose: determine RNA expression differences in an unbiased fashion between UPS tumors derived from LSL-KrasG12D;Trp53-/- (KP) mice, and UPS tumors derived from LSL-KrasG12D;Trp53-/-;Epas1-/- (KPH2) mice. Epas1 encodes HIF-2alpha protein. Overall design: RNA-seq was performed on KP (n = 4) and KPH2 (n = 4) derived UPS tumors using Illumina HiSeq 2000.
Epigenetic re-expression of HIF-2α suppresses soft tissue sarcoma growth.
No sample metadata fields
View SamplesZinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon.
Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain.
Specimen part
View SamplesCongenital heart defects (CHDs) occur in 0.51% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca2+ signaling is known to be essential formany aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP3Rs), which are intracellular Ca2+ release channels on the endo/sarcoplasmic reticulum that mediate Ca2+ mobilization. Mouse embryos that are double mutant for IP3R type 1 and type 3 (IP3R1/IP3R3/) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis ofmesodermal cells in the SHF. Gene expression analyses suggest that IP3R-mediated Ca2+ signalingmay involve, at least in part, theMef2CSmyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP3R type 1 and type 3 may play a redundant role in the development of the SHF.
Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field.
No sample metadata fields
View SamplesWe found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel, a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells.
Global gene expression changes including drug metabolism and disposition induced by three-dimensional culture of HepG2 cells-Involvement of microtubules.
No sample metadata fields
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
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