p63, like its homologue, the tumor suppressor p53, is also able to induce apoptosis in several cancer cell types. p53 family proteins are composed of three characteristic domains which are: 1) an N-terminal transactivation domain (TAD); 2) a central DNA-binding domain (DBD); and 3) an oligomerization domain (OD). In this study, we constructed recombinant adenoviruses containing hybrid genes composed of fragments of p53 and TAp63 genes by connecting coding sequences of their three functional domains. The potency of tumor growth suppression of these hybrid molecules was evaluated using in vitro and in vivo models. One of the p53-p63 hybrid molecules, p63-53O, was observed to be the most potent activator of human cancer cells to apoptosis when compared to the p53, TAp63 or several alternative p53-p63 hybrid molecules. p63-53O hybrid is composed of TAD and DBD of TAp63 and OD of p53. In an effort to identify specific targets regulated by pro-apoptotic hybrid p63-53O, we next performed Affymetrix Genechip analysis and compared expression patterns in a human osteosarcoma cell line Saos-2 transfected separately with Ad-p53, Ad-TAp63 and Ad-p63-53O.
A novel approach to cancer treatment using structural hybrids of the p53 gene family.
Cell line
View SamplesThe p53 family consists of three members, p53, p73, and p63. These proteins share a high degree of amino-acid sequence similarity and major functional domains. The p53 gene, the first member of the family to be identified, is the most frequent target gene for genetic alterations in human cancers. In contrast, p73 and p63 are mainly involved in normal development and differentiation. These differences among the p53 family are likely to depend on activation or repression of different sets of target genes. In this study, to identify targets specifically regulated by p73, we performed microarray analysis and compared expression patterns in a human steosarcoma cell line Saos-2 infected separately with p53 and TAp73beta expressing adenovirus.
p53 family members regulate the expression of the apolipoprotein D gene.
No sample metadata fields
View SamplesRedox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic and abiotic induced redox signals. Inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Overexpressor (oe) lines are impaired in root and shoot development, light sensitive and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica which reduces ROS accumulation locally in roots and systemically in shoots, and by antioxidants and ROS inhibitors which scavenge ROS. More than 850 stress-, redox-, ROS regulated-, ROS scavenging-, defense-, cell death- and senescence-related genes are regulated by RRTF1, ~ 30% of them have ROS related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box and GCC-box like sequences in the promoter of RRTF1-responsive genes. Upregulation of RRTF1 by stress stimuli as well as H2O2 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenetically related RAP2.6, which contains GCC-box like sequene in its promoter, but RAP2.6 oe lines do not accumulate higher ROS levels. RRTF1 stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the highly conserved RRTF1 rapidly, transiently and systemically induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals. Necrotrophs stimulate RRTF1 expression, while symbiotic interactions of Arabidopsis with (hemi)-biotrophs and P. indica do not affect or repress RRTF1 expression.
High REDOX RESPONSIVE TRANSCRIPTION FACTOR1 Levels Result in Accumulation of Reactive Oxygen Species in Arabidopsis thaliana Shoots and Roots.
Specimen part
View SamplesRedox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic and abiotic induced redox signals. Inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Overexpressor (oe) lines are impaired in root and shoot development, light sensitive and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica which reduces ROS accumulation locally in roots and systemically in shoots, and by antioxidants and ROS inhibitors which scavenge ROS. More than 850 stress-, redox-, ROS regulated-, ROS scavenging-, defense-, cell death- and senescence-related genes are regulated by RRTF1, ~ 30% of them have ROS related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box and GCC-box like sequences in the promoter of RRTF1-responsive genes. Upregulation of RRTF1 by stress stimuli as well as H2O2 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenetically related RAP2.6, which contains GCC-box like sequene in its promoter, but RAP2.6 oe lines do not accumulate higher ROS levels. RRTF1 stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the highly conserved RRTF1 rapidly, transiently and systemically induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals. Necrotrophs stimulate RRTF1 expression, while symbiotic interactions of Arabidopsis with (hemi)-biotrophs and P. indica do not affect or repress RRTF1 expression.
High REDOX RESPONSIVE TRANSCRIPTION FACTOR1 Levels Result in Accumulation of Reactive Oxygen Species in Arabidopsis thaliana Shoots and Roots.
Age, Specimen part
View SamplesWe have demonstrated that allergic airway inflammation (induced by an ovalbumin sensitization and aerosol challenge protocol) decreases lung bacterial burden following lung infection with Klebsiella pneumoniae. The goals of this study are to indentify novel targets that are expressed during allergic airway inflammation in this model that contribute to enhanced lung bacterial immunity. Overall design: We isolated total RNA from the lungs of 4 groups of mice at both 0 hours (pre-infection) and 6 hours post-infection. WT and STAT6KO (BALB/c) mice were intraperitoneally sensitzed with alum or ovalbumin (OVA)-alum on day -18. Alum injected mice were not subsequently exposed to OVA aerosol. OVA-alum injected mice underwent aerosol sensitization on days -4, -3, -2, and -1. On day 0, four groups of mice were harvested (pre-infection). These included WT-ALUM, WT-OVA, STAT6KO-ALUM, and STAT6KO-OVA. On day 0, four groups of mice were infected with 10^4cfu of Klebsiella and then lungs were removed at 6 hours post-infection. These groups included WT-ALUM-KP, WT-OVA-KP, STAT6KO-ALUM-KP, and STAT6KO-OVA-KP. The right lung was removed for RNA isolation. Each group contained between 4 and 5 mice.
Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.
No sample metadata fields
View SamplesOncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role of this silencing in oncogenesis is not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting DNA demethylase TET oncogene family member 1 (TET1) via the C/EBP transcription factor. After oncogenic EGFR inhibition, TET1 binds to tumor suppressor promoters and induces their re-expression via active DNA demethylation. Ectopic expression of TET1 potently inhibits lung and glioblastoma tumor growth, and TET1 knockdown confers resistance to EGFR inhibitors in lung cancer cells. Lung cancer samples exhibited reduced TET1 expression or TET1 cytoplasmic localization in a majority of cases. Collectively, these results identify a conserved pathway of oncogenic EGFR-induced DNA methylation-mediated transcriptional silencing of tumor suppressors, which may have therapeutic benefit for oncogenic EGFR-mediated lung cancers and glioblastomas.
Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells.
Cell line
View SamplesThe effect of cyclic mecanical stretch on cardiac gene expression was studied in neonatal rat ventricular myocytes (NRVMs).
Mechanical stretch induced transcriptomic profiles in cardiac myocytes.
Treatment
View SamplesThe rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix.
Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons.
Cell line
View SamplesThe aim of this study was to determine how gene expression is changed after arsenite-induced malignant transformation of prostate epithelial cells.
Coordinate H3K9 and DNA methylation silencing of ZNFs in toxicant-induced malignant transformation.
Specimen part, Cell line, Treatment
View SamplesInhibition of miR-361-3p by locked nucleic acid (LNA)/DNA antisense oligonucleotide markedly suppressed the growth of GFP-SAS cells.
MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma.
Specimen part, Cell line
View Samples