Mice lacking the function of the PcG protein CBX2 (also known as M33) show defects in gonadal, adrenal, and splenic development. In particular, XY knockout mice develop ovaries but not testes, and the gonads are hypoplastic in both sexes.
Cbx2, a polycomb group gene, is required for Sry gene expression in mice.
Specimen part
View SamplesSeries of samples studying effect of knock out Emx2 in urogenital epithelium of mouse embryos at E10.5.
Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads.
No sample metadata fields
View SamplesSharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-B signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here, we report novel mechanisms of HCC progression through Sharpin overexpression. Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in stably Sharpin-expressing cells. Versican expression increased in the majority of HCC tissues and knocking down of versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of versican transcription synergistically with Wnt/-catenin pathway activation. Furthermore, Sharpin overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes versican expression synergistically with the Wnt/-catenin pathway, potentially contributing to HCC development. A Sharpin/versican axis could be an attractive therapeutic target for this currently untreatable cancer.
Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.
Specimen part
View SamplesEpigenetic gene regulation in various oncogenic pathways is currently an important focus of cancer research. The PI3K pathway plays a pivotal role in hepatocellular carcinoma, but the significance of histone modification in the PI3K pathway-dependent hepatotumorigenesis remains unknown.
Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.
Specimen part
View SamplesTo find direct or indirect targets of Ad4BP/SF-1, RNA profiles of Y-1 cells were obtained with or without siRNA for Ad4BP/SF-1.
Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1.
No sample metadata fields
View SamplesTransforming growth factor (TGF)- plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF--induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF--induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
Specimen part
View SamplesDNA methylation has been considered to play an important role during myogenic differentiation. In terminal differentiation of myoblasts, chronological alteration of DNA methylation status was poorly understood. Using Infinium HumanMethylation450 BeadChips, we validated genome wide DNA methylation profiles of human myoblast differentiation models. To investigate correlation between DNA methylation and gene expression, we also assessed gene expression of myoblasts with GeneChip Human Genome U133 Plus 2.0 array.
DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation.
Sex, Age, Race
View SamplesIn order to gain insight into the molecular events operating downstream of canonical wnt-signaling in myoblasts, we compared by microarray analysis the transcriptome of myoblast cultured for 4 hours in the presence and absence of Wnt3a.
A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
Specimen part, Cell line, Treatment
View SamplesWe determined and analyzed the effect of TTF-1/NKX2-1 on Smad3/Smad4 binding sites by ChIP-sequencing.
A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
Specimen part, Cell line
View Samples