Project description:To gain insight into the functional mechanisms of an RXR agonist HX630 in murine pituitary corticotroph tumor cells (AtT20 cell), especially concerning cell proliferation and apoptosis, we conducted whole genome microarray analysis to identify gene expression patterns, networks, and pathways in AtT20 cells treated with HX630 at 10 μM for 48 hr. 2,173 up-regulated and 3,169 down-regulated genes were identified that demonstrated fold-changes of at least 1.5 and a P-value <0.01 in AtT20 cells with HX630 at 10 uM compared with control. Both the up- and down-regulated differentially expressed genes were submitted to IPA, which groups significant genes according to biological processes in which they function, and identifies various functions, networks, and pathways. These analyses showed that the categories of the biological functions and diseases significantly regulated by HX630 were associated with cell death, growth and cancer. Furthermore, it was identified that a gene network associated with caspase 3 was significantly induced by HX630.These data indicated that HX630 induced cell death and suppressed cell growth in AtT20 cells, consistent with the results of in vitro studies.
Project description:To gain insight into the functional mechanisms of an RXR agonist HX630 in murine pituitary corticotroph tumor cells (AtT20 cell), especially concerning cell proliferation and apoptosis, we conducted whole genome microarray analysis to identify gene expression patterns, networks, and pathways in AtT20 cells treated with HX630 at 10 M-NM-<M for 48 hr. 2,173 up-regulated and 3,169 down-regulated genes were identified that demonstrated fold-changes of at least 1.5 and a P-value <0.01 in AtT20 cells with HX630 at 10 uM compared with control. Both the up- and down-regulated differentially expressed genes were submitted to IPA, which groups significant genes according to biological processes in which they function, and identifies various functions, networks, and pathways. These analyses showed that the categories of the biological functions and diseases significantly regulated by HX630 were associated with cell death, growth and cancer. Furthermore, it was identified that a gene network associated with caspase 3 was significantly induced by HX630.These data indicated that HX630 induced cell death and suppressed cell growth in AtT20 cells, consistent with the results of in vitro studies. AtT20 cells grown to 50 % confluence in regular medium in 12-multiwell plates were incubated either without or with HX630 at 10 M-NM-<M in DMEM supplemented with 1 % stripped FBS media for 48 hr. The cells were then lysed and their total RNAs were isolated for microarray analysis.
Project description:Transcription factor Creb3l1 is a non-classical ER stress molecule that is emerging as an important component for cellular homeostasis, particularly within cell-types with high peptide secretory capabilities. We have previously shown that Creb3l1 serves an important role in body fluid homeostasis through its transcriptional control of the gene coding for antidiuretic hormone arginine vasopressin in the neuropeptide rich magnocellular neurons of the supraoptic nucleus. To identify other genes regulated by transcription factor Creb3l1 in secretory cells, we performed RNA-sequencing of Creb3l1 knockdown anterior pituitary mouse corticotroph cell line AtT20.
2020-04-03 | GSE147978 | GEO
Project description:microarray analysis of human corticotroph tumor
Project description:CGH array analysis was performed on 195 fresh-frozen pituitary tumors (56 gonadotroph, 11 null-cell, 56 somatotroph, 39 lactotroph and 33 corticotroph), with 5 years post-surgery follow-up
Project description:The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice is dependent on LXR and correlates with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the role of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily increases the genomic binding of RXR, whereas the LXR agonist T0901317 greatly increases both LXR and RXR binding. Functional annotation of putative direct LXR target genes revealed a significant association with classical LXR-regulated pathways as well as PPAR signaling pathways, and subsequent ChIP-seq mapping of PPARM-NM-1 binding demonstrated binding of PPARM-NM-1 to 71-88% of the identified LXR:RXR binding sites. Sequence analysis of shared binding regions combined with sequential ChIP on selected sites indicate that LXR:RXR and PPARM-NM-1:RXR bind to degenerate response elements in a mutually exclusive manner. Together our findings suggest extensive and unexpected cross-talk between hepatic LXR and PPARM-NM-1 at the level of binding to shared genomic sites LXR, RXR, PPARalpha and RNA Polymerase II ChIP-seq on livers from female C57BL/6 wild-type and/or LXRM-NM-1/M-NM-2-deficient mice (13 weeks of age, n=1) treated by oral gavage once daily for 14 days with the RXR agonist bexarotene (100 mg/kg body weight [mpk], in 1% carboxymethylcellulose), the LXR agonist T0901317 (T09, 30 mpk) or vehicle alone.
Project description:The pituitary tumors (PA) arise in adenohypophyseal cells and are the second most common tumor in central nervous system. Reflective of their monoclonal cell of origin these tumors could be classified according to the hormone that they produce. The mutational and copy number variation burden in these tumors are scarce, indicating other molecular events are involved in pituitary tumorigenesis. Here we show throughout transcriptome and methylome analysis that there are three readily distinctive molecular signatures. The first group is comprised by the gonadotropes, null cell and silent corticotroph PA, the second group comprised by ACTH PA and the group cluster together the TSH-, PRL- and GH- PA. These groups showed CACNA2D4, EPHA4 and SLIT1 gene up-regulation, respectively. Pathway enrichment analysis support the previous observations. The calcium signaling pathway is characteristic for gonadotropes null cell and silent corticotroph, the Renin-Angiotensin system for the ACTH PA and the Fatty acid metabolisms for the TSH-, PRL-, GH- cluster. The analysis of scRNA-seq from non-tumoral pituitary tissue revealed that these three groups originate since the pituitary development/embryogenesis. The immune cell infiltration landscape revealed that PA could be potentially infiltrated by NK and mast cells. Taken together these results correlate with the expression of the NR5A1, TBX19 and POU1F1 transcription factors, which drive pituitary embryogenesis and theoretically tumorigenesis and potentially indicates three divergent cell precursors cells. We used microarrays to detail the molecular alteration in PA compared to non-tumoral gland.
Project description:The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice is dependent on LXR and correlates with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the role of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily increases the genomic binding of RXR, whereas the LXR agonist T0901317 greatly increases both LXR and RXR binding. Functional annotation of putative direct LXR target genes revealed a significant association with classical LXR-regulated pathways as well as PPAR signaling pathways, and subsequent ChIP-seq mapping of PPARα binding demonstrated binding of PPARα to 71-88% of the identified LXR:RXR binding sites. Sequence analysis of shared binding regions combined with sequential ChIP on selected sites indicate that LXR:RXR and PPARα:RXR bind to degenerate response elements in a mutually exclusive manner. Together our findings suggest extensive and unexpected cross-talk between hepatic LXR and PPARα at the level of binding to shared genomic sites