E-GEOD-29494
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA141657
PROVIDER: E-GEOD-29494 | ExpressionAtlas | 2025-01-24
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-29494-analysis-methods.tsv | Tabular | |||
| E-GEOD-29494-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-29494-configuration.xml | Xml | |||
| E-GEOD-29494-percentile-ranks.tsv | Tabular | |||
| E-GEOD-29494.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 53 |
Similar Datasets
Project description:Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major cause of autosomal recessive parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor. Consistent with this, the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we show that parkin expression is dramatically reduced in glioma cells, which correlates with increased cancer mortality. We further show that restoration of parkin expression in these cells promotes their arrest at G1 phase and significantly mitigates their proliferation rate both in vitro and in vivo. Notably, the level of cyclin D1, but not cyclin E, is reduced in parkin-expressing glioma cells. Moreover, parkin expression also leads to a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. Supporting this, cells derived from parkin null mouse exhibit increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divide significantly faster compared to their wild type counterparts. Importantly, analysis of parkin pathway activation revealed its predictive power for survival outcome of glioma patients. Taken together, our study provides a mechanism by which parkin exerts its tumor suppressor function and a signature pathway of parkin that is of potential prognostic value. Total RNA obtained from U-87MG cells stably expressing parkin or vector alone. Replicate arrays were performed for each of the 3 vector and parkin-expressing U-87MG clones.
2012-03-15 | E-GEOD-29494 | biostudies-arrayexpress
Project description:Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
2012-03-15 | GSE29494 | GEO
Project description:Akt signalling leads to stem cell activation and promotes tumour development in epidermis.
2015-07-16 | E-GEOD-48522 | ExpressionAtlas
Project description:ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [expression]
2015-08-04 | E-GEOD-57133 | ExpressionAtlas
Project description:Bidkhori2012 - normal EGFR signalling
The paper describes and compares two models on EGFR signalling between normal and NSCLC cells. Moreover, it is shown that ERK (MAPK), STAT and Akt factor's activation pattern are different between normal and NSCLA models. This model corresponds to EGFR signalling in normal cells.
Created by The MathWorks, Inc. SimBiology tool, Version 3.3
This model is described in the article:
Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression.
Bidkhori G, Moeini A, Masoudi-Nejad A
PloS one [2012, 7(10):e48004]
Abstract:
EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.
This model is hosted on BioModels Database
and identified
by: MODEL1304020000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000452 | BioModels
Project description:Bidkhori2012 - EGFR signalling in NSCLC
The paper describes and compares two models on EGFR signalling between normal and NSCLC cells. Moreover, it is shown that ERK (MAPK), STAT and Akt factor's activation pattern are different between normal and NSCLA models. This model corresponds to EGFR signalling in NSCLA cells.
Created by The MathWorks, Inc. SimBiology tool, Version 3.3
This model is described in the article:
Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression.
Bidkhori G, Moeini A, Masoudi-Nejad A
PloS one [2012, 7(10):e48004]
Abstract:
EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.
This model is hosted on BioModels Database
and identified
by: MODEL1304020001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000453 | BioModels
Project description:Glioblastoma stem cells (GSCs) fate is controlled by environmental cues, among which cytokines play a crucial role. The transforming growth factor β (TGFβ) family signaling pathways controls GSCs. On one hand, TGFβ promotes cell proliferation in GBM, it induces the expression of platelet-derived growth factor-B (PDGFB). Moreover, TGFβ, via its signaling mediators Smad2/3, induces the expression of the cytokine leukemia inhibitory factor (LIF) and Sox4, which in turn enhances the expression of the stem cell transcription factor Sox2; this increases the self-renewal capacity of the GSCs and their stemness characteristics, and enhances the GSC tumor-initiating potential. On the other hand, Bone morphogenic proteins (BMPs) are known to promote GSC differentiation towards the astrocytic phenotype. To further understand which genes are regulated by TGFβ and BMP7 in GSCs we performed a microarray in the Affymetrix HTA2 platform in three different glioblastoma cell line, U2987, and two patient-derived glioblastoma stem cells, U3031MG and U3034MG, in the presence or absence of 5 ng/ml of TGFβ or 30 ng/ml BMP7 for 24 h, three biological replicates per condition.
2020-09-01 | E-MTAB-9076 | biostudies-arrayexpress
Project description:Primary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling. Rictor/mTORC2 deletion inhibits Akt signaling, causing a significant delay in p53-mutant driven glioma formation. Unexpectedly, Rictor/mTORC2 loss promotes p53-mutant driven medulloblastomas with unique features of pediatric SHH medulloblastoma. Mechanistically, Rictor/mTORC2 loss inhibits the generation of glioma precursor cells from neural stem/progenitor cells in the adult brain, while causing a delay in differentiation of granule cell precursors in the developing brain, a cell-of-origin of SHH medulloblastoma.
2018-06-01 | GSE78895 | GEO
Project description:AMBRA1 is a tumour suppressor protein that functions as a substrate receptor in the ubiquitin conjugation system and regulates the stability of D-type cyclins and cell proliferation. Here, we present the cryo-EM structure of cyclin D1 bound AMBRA1-DDB1 complex at 3.55 Å resolution. The structure reveals a substrate interaction surface on the AMBRA1 WD40 domain that specifically binds to the C-terminal region of D-type cyclins. This interaction is dependent on the phosphorylation of Thr286 residue in the C-terminal phosphodegron site of D-type cyclins. The phosphodegron motif folds into a turn-like conformation followed by a 310 helix that promotes its assembly with AMBRA1. Additionally, we show that AMBRA1 mutants, which are defective in cyclin D1 binding, lead to cyclin D1 accumulation and DNA damage. Understanding the AMBRA1-D-type cyclins structure enhances the knowledge of the molecular mechanisms that govern the cell cycle control and may lead to new therapeutic approaches for cancers linked to abnormal cyclin D activity.
2025-04-17 | PXD062122 | Pride
Project description:HIF1α promotes glioblastoma cell proliferation and tumorigenesis under hypoxia conditions, leading to poor prognosis; however, none of the targeted therapies of HIF1α for glioblastoma is success nowadays. Therefore, we focused to look for the reason and wondered whether HIF2α contributed GBM growth. We did gene-chip and found that HIF2α contributed to the malignant progression of glioblastoma while blocking of HIF1α. Furthermore, our results revealed knock-out of HIF1α and HIF2α simultaneously improved the chemo-sensitization significantly. Moreover, miR-210-3p induced HIF1α expression but inhibited HIF2α, which meant the existence of regulation of cycle between HIF1α/HIF2α and miR-210-3p. Traditional studies have proved EGF as an upstream gene regulator of HIF1α in hypoxia conditions through EGFR-PI3K/AKT-mTOR signaling pathway. However, in this study, besides the signaling pathways mentioned above, we found the upstream regulators HIF1α and HIF2α also promoted EGF with the binding regions AGGCGTGG and GGGCGTGG. Briefly, in hypoxia microenvironment HIF1α/HIF2α-miR210-3p network promotes malignant progression of glioblastoma through EGFR-PI3K/AKT-mTOR signaling pathway with a positive feedback.
2020-11-24 | GSE142719 | GEO