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 SamplesComparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of MSI2 in vivo
Transformation of the intestinal epithelium by the MSI2 RNA-binding protein.
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 SamplesComparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of Msi1 in vivo
The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.
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 SamplesC-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)B signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-B. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1 resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-B, and that CCL2 produced by this pathway contributes to tumor progression.
Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages.
Cell line
View SamplesC-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)B signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-B. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1 resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-B, and that CCL2 produced by this pathway contributes to tumor progression.
Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages.
Cell line
View SamplesC-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)B signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-B. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1 resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-B, and that CCL2 produced by this pathway contributes to tumor progression.
Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages.
Cell line
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 Samples