Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of Δ122p53, a Δ133p53α-like isoform, on global gene expression in response to DNA damage in mouse splenocytes

ABSTRACT: The p53 protein is a pivotal tumor suppressor that is frequently mutated in many human cancers, although precisely how p53 prevents tumors is still unclear. To add to its complexity several isoforms of human p53 have now been reported. The Δ133p53α isoform is generated from an alternative transcription initiation site in intron 4 of the p53 gene (TP53) and lacks the N-terminus. Elevated expression of Δ133p53α has been observed in a variety of tumors. To explore the functions of Δ133p53α, we created a mouse expressing an N-terminal deletion mutant of p53 (Δ122p53) that corresponds to Δ133p53α. Δ122p53 mice show decreased survival and a different and more aggressive tumor spectrum compared to p53 null mice, implying that Δ122p53 is a dominant oncogene. Consistent with this, Δ122p53 also confers a marked proliferative advantage on cells and reduced apoptosis. In addition to tumor development Δ122p53 mice show a profound pro-inflammatory phenotype having increased serum concentrations of interleukin (IL)-6 and other pro-inflammatory cytokines and lymphocyte aggregates in the lung and liver as well as other pathologies. Based on these observations, we propose that human Δ133p53α also functions to promote cell proliferation and inflammation, one or both of which contribute to tumor development. Total RNA was isolated from pooled splenocytes from four 5-6 week old mice with different p53 status (wild type, p53-/-, or Δ122p53) subjected to DNA damaging or control treatments.

ORGANISM(S): Mus musculus

SUBMITTER: Aaron Jeffs

PROVIDER: E-GEOD-27586 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

The effect of Δ122p53, a Δ133p53α-like isoform, on global gene expression in response to DNA damage in mouse splenocytes

Project description:The p53 protein is a pivotal tumor suppressor that is frequently mutated in many human cancers, although precisely how p53 prevents tumors is still unclear. To add to its complexity several isoforms of human p53 have now been reported. The Δ133p53α isoform is generated from an alternative transcription initiation site in intron 4 of the p53 gene (TP53) and lacks the N-terminus. Elevated expression of Δ133p53α has been observed in a variety of tumors. To explore the functions of Δ133p53α, we created a mouse expressing an N-terminal deletion mutant of p53 (Δ122p53) that corresponds to Δ133p53α. Δ122p53 mice show decreased survival and a different and more aggressive tumor spectrum compared to p53 null mice, implying that Δ122p53 is a dominant oncogene. Consistent with this, Δ122p53 also confers a marked proliferative advantage on cells and reduced apoptosis. In addition to tumor development Δ122p53 mice show a profound pro-inflammatory phenotype having increased serum concentrations of interleukin (IL)-6 and other pro-inflammatory cytokines and lymphocyte aggregates in the lung and liver as well as other pathologies. Based on these observations, we propose that human Δ133p53α also functions to promote cell proliferation and inflammation, one or both of which contribute to tumor development.

2011-03-02 | GSE27586 | GEO

Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas

Project description:We used gene transcript profiling to gain a deeper understanding of the role of FBXW7 in tumor development and to determine the influence of mTOR inhibition by rapamycin on tumor transcriptome and biological functions. In comparison to tumors from p53 single heterozygous (p53+/-) mice, we find that tumors from Fbxw7/p53 double heterozygous (Fbxw7+/-p53+/-) mice show significant deregulation of cholesterol metabolic processes independent of rapamycin treatment, while cell cycle related genes were upregulated in tumors from placebo treated Fbxw7+/-p53+/- mice, but not in tumors from rapamycin treated Fbxw7+/-p53+/- mice. On the other hand, tumors from rapamycin treated Fbxw7+/-p53+/- mice were enriched for genes involved in the integrated stress response, an adaptive mechanism to survive in stressful environments. p53+/â and p53+/âFbxw7+/â mice were generated by crossing p53-/- mice with Fbxw7+/- mice. At 5 weeks of age, mice were exposed whole-body to a single dose of 4 Gy X-ray irradiation. Mice were divided randomly into two groups and treated with rapamycin or placebo. RNA was isolated from thymic lymphomas.

2015-10-31 | E-GEOD-71975 | biostudies-arrayexpress

Transcription profiling by array of mouse macrophage cell cultures from C57BL/6 or CBA/Ca strains after exposure to 4 Gy irradiation

Project description:Macrophages were produced from bone marrow cell suspensions from the femurs of five C57BL/6 or CBA/Ca mice by culture for 7 days in modified Eagles medium supplemented with 25% pre-tested horse serum and 25% pre-tested conditioned medium from the L929 cell line as a source of CSF-1. For each experiment, five flasks were exposed to 4Gy irradiation at a dose rate of 0.5Gy/min at room temperature using a CIS Bio International 637 Caesium irradiator and five flasks were sham-irradiated. RNA was extracted 24 hours later for analysis on MOE430-2 affymetrix arrays

2007-12-01 | E-MEXP-1291 | biostudies-arrayexpress

IDH1R132H activity in glioma cell lines and tumnor tissue (2HG)

Project description:We developed genetically engineered mice to generate brain tumors with especific genetic lessions. The animals were split in three groups: NRAS, P53 knockdown, IDH1-R132H and ATRX knock down (NPAID); NRAS, P53 knockdown, IDH1-R132H (NPI); NRAS, P53 knockdown, (NshP53). From these tumor we obtain and culture tumor cells growth like neurospheres and attached cells.

2015-03-05 | ST000312 | MetabolomicsWorkbench

Mutant p53 Increases Incidence and Promotes Progression of Mammary Carcinomas in Mice

Project description:In human breast cancer, mutations in the p53 gene are associated with poor prognosis, suggesting a mutant p53 “gain of function”. To study this phenomenon, we co-expressed mutant p53R270H in mice in which SV40 early proteins initiate the development of mammary adenocarcinomas in descendants of mammary epithelial cells that survived involution (WAPT-mice). This model allows the characterization of mammary carcinomas that developed in the absence or presence of mutant p53, while the endogenous wild-type p53 is functionallycompromised. Co-expression of mutant p53 significantly aggravated the phenotype of bitransgenic mice, as evidenced by a higher tumor incidence, a worse clinical staging and histological grading, as well as an enhanced invasiveness of the tumors, and more frequent pulmonary metastasis. Our data indicate that mutant p53 does not exert this effect by increasing genomic instability. On the contrary, lower grade tumors in WAP-T mice generally accumulated more amplifications of pro-survival genes than the corresponding tumors in bitransgenic animals, suggesting that mutant p53 can compensate for such genetic alterations by alternative mechanisms, possibly by its transcriptional activities, and thereby facilitate tumor formation. As a common feature and associated with their enhanced invasiveness, high grade tumors showed high level amplification of the Met-locus. Keywords: mutant p53, SV40 early proteins, tumor progression, tumor grade, tumor stage, mammary carcinoma, animal model, Met

2007-12-31 | GSE7135 | GEO

Transcription profiling of mouseB-cell lymphomas with defined genetic alterations in p53 or p73

Project description:Induction of apoptosis by the tumor suppressor p53 is known to protect from Myc-driven lymphomagenesis. The p53 family member p73 is also a pro-apoptotic protein, which is activated in response to oncogenes like Myc. We therefore investigated whether p73 provides a similar protection from Myc-driven lymphomas as p53. To generate B-cell lymphomas with defined genetic alterations in p53 or p73, we crossed the Eµ-Myc transgenic to mice heterozygous for germ-line deletions in p53 (p53+/) or p73 (p73+/-). Lymphomas which have spontaneously developed in Eµ-Myc transgenic animals with the genotypes p53+/+, p53+/-, p73+/+, p73+/- or p73-/- were isolated when the animals were moribund and further processed for gene expression profiling with 22.5K cDNA microarrays.

2008-12-05 | E-MEXP-1620 | biostudies-arrayexpress

Genomic profiles of mouse liver tissue harboring deletion of RB and/or p53, untreated or post-hepatocarcinogen treatment [CGH data]

Project description:The retinoblastoma (RB) and p53 tumor suppressors are critical regulators of the cell cycle with profound impact on both normal cell biology and disease etiology. In the context of human cancers, compound inactivation of RB and p53 is a frequent occurrence; however, the cooperation of these tumor suppressors in driving tumorigenesis has proven to be intricate and dependent on both the tissue and type of cancer. Hepatocellular carcinoma (HCC) is a highly complex disease characterized by numerous molecular abnormalities (e.g. p53, RB, TGFβ) and chromosomal aberrations associated with environmental factors (e.g. Hepatitis B/C Virus, Aflatoxin B1). Despite extensive research, how each of these facets of disease development cooperates in promoting tumorigenesis is ultimately unknown. In the current study, we present a mouse model of liver tumorigenesis, in which the impact of RB and p53 loss is modified by the tissue environment. While loss of RB and p53 promotes deregulation of transcriptional programs associated with advanced disease, these changes are not sufficient to drive spontaneous tumorigenesis in the liver. However, in response to carcinogen-induced damage, distinct and cooperative roles of RB and p53 are revealed, which critically impact cell cycle control, checkpoint response, genome stability, and ultimately tumor development. Mice that are transgenic for Cre recombinase under the albumin promoter and harboring loxP sites within the Rb and/or p53 genes. For gene expression microarray analysis, mice were aged to 14 days, and treated for 24 hours with diethylnitrosamine (DEN) or saline as a control. For CGH analysis, mice were aged to 6 months post-DEN treatment. Liver tissue was obtained from dissected tumors and compared to normal liver tissue of 6-month old, saline-treated littermates. CGH analysis includes 5 individual tumor samples and 2 control samples (each consisting of a pool of 3 normal mouse liver DNA).

2011-09-19 | E-GEOD-29847 | biostudies-arrayexpress

2 hydroxyglutarate prodution in neurospheres from IDH1 mouse glioma model #2

Project description:Evaluation of 2HG and a-ketoglutarate in tumor neurospheres (NS) genertated from the mice brain tumors haboring specific genetic lesions: NRAS overexpression, p53 knockdown plus or minus IDH1 mutated and ATRX knockdown.

2017-07-14 | ST000820 | MetabolomicsWorkbench

Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and metastasis of carcinogen-induced colorectal tumors

Project description:Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC) specific deletion of p53, we demonstrate that single loss of p53 is not sufficient to initiate intestinal tumorigenesis, but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. While during the initiation stage p53 controls DNA damage and IEC survival, during tumor progression, loss of p53 is associated with the formation of an inflammatory microenvironment and activation of NF-kB and Stat3. Thus, we propose a novel p53 controlled tumor suppressive function that is independent of its well-established role in cell cycle regulation, apoptosis and senescence. 4 AOM induced cancers derived from Tp53DEIC mice were isolated and DNA was extracted. These were compared to genomic DNA isolated from healthy littermate control animals. Agilent Mouse 4x180K arrays were used (Design ID 27411).

2011-03-23 | E-GEOD-28129 | biostudies-arrayexpress

Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas

2015-10-31 | GSE71975 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data