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 SamplesTo identify factors involved in glioma-initiating cells (GICs), we compared gene expressions between GIC-like cells and non-GICs.
Combination of a ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells.
Specimen part
View SamplesTo identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part
View SamplesTo identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, 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 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 SamplesA promoter associated lncRNA Myoparr is involved in the regulation of skeletal muscle atrophy caused by denervation. However, the molecular mechanism by which Myoparr regulates the expression of downstream genes in skeletal muscle tissue is largely unknown. Thus, we compared the Transcriptome profiles of denervated tibialis anterior muscles transfected with control or Myoparr shRNA.
Long Non-Coding RNA <i>Myoparr</i> Regulates GDF5 Expression in Denervated Mouse Skeletal Muscle.
Sex, Specimen part, 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.
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