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GSE57801
Mus musculus, Drosophila melanogaster
71 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
Publication Title
Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina HiSeq 2000
Description
Understanding the mechanisms by which cells respond to chemotherapeutics is key to identifying means to improve therapy effiicacy while reducing systemic toxicity of these widely used classes of drugs. While determining the role of NRF2-GSH and ER stress in cells exposed to alkylating compounds such as methyl-methanesulfonate (MMS), we asked if these pathways could also be a general cell damage response relevant to other clinically used chemotherapeutics or if it is an alkylation specific response. With this intent, we performed RNA sequencing of MDA-MB231 breast cancer and U2OS osteosarcoma cells lines treated for 8 hours with a topoisomerase II inhibitor etoposide (20 µM), the antimitotic beta-tubulin-interacting drug paclitaxel (0.2 µM), doxorubicin (1 µM) and compared to MMS (40 µg/mL) treated cells. Doses represent IC50 level after 72 hours exposure. We observed that even though non-alkylating drugs, especially etoposide, caused an increase in the mRNA expression of some NRF2 and ER stress signaling markers, the number and magnitude of upregulation of genes markers in either pathway was more pronounced in alkylation treatments compared to other drugs. This indicates that alterations in NRF2 and ER stress pathways could be more likely associated with differential sensitivity to alkylating chemotherapies. Overall design: MDA-MB231 breast cancer and U2OS osteosarcoma cells lines were treated with the 72 h IC50 dose of etoposide (20 µM), paclitaxel (0.2 µM), doxorubicin (1 µM) or MMS (40 µg/mL) for 8 h, and RNA was extracted and analyzed.
Publication Title
Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Molecular targeted compounds are emerging as important component to improve the efficacy of classical chemotherapeutics. In this study, we tested whether using low dose sorafenib to reduce off target inhibitions of kinases impacts the antitumor effect of alkylating agents in breast cancer models. Overall design: MDA-MB231 cells were treated with 1 µM sorafenib, 40 µg/mL MMS, or pre-incubated with 1 µM sorafenib for 12 h followed by 40 µg/mL MMS, each in two independent experiments. RNA was harvested 8 and 24 h, or post MMS treatment for combination treatment.
Publication Title
Sorafenib improves alkylating therapy by blocking induced inflammation, invasion and angiogenesis in breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
These data include RNA Seq data generated from wild type and Eed Ko intestinal crypts from AhCre and AhCreEedf/f mice. Overall design: Total RNA extracted from wild type and Eed Ko intestinal crypts.
Publication Title
PRC2 preserves intestinal progenitors and restricts secretory lineage commitment.
Sample Metadata Fields
Cell line, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were determined in XVE-14 and wild-type seedlings induced for 45 min b-estradiol in order to identify the genes early regulated by EBE transcription factor.
Publication Title
EBE, an AP2/ERF transcription factor highly expressed in proliferating cells, affects shoot architecture in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The aim was to identify early target genes of the senescence-associated transcription factor: ORS1. For this purpose we used DEX-inducible system and studied the expression profile 5h after treatment using Affymetrix microarray.
Publication Title
ORS1, an H₂O₂-responsive NAC transcription factor, controls senescence in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a CRC related signature of differentially expressed genes discriminating patients Responder and Non Responder to radiochemotherapy
Publication Title
A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Spleen and lymph node dendritic cells have a differential capacity do induce and retain iTreg cells. Therefore we performed a comparative analysis of the dendritic cells derived from these two compartments to identify the responsible genes
Publication Title
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.
Sample Metadata Fields
Specimen part
View Samples