Homo sapiens
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PROVIDER: PRJNA103145 | ENA |
REPOSITORIES: ENA
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Project description:The abstract of the associated publication (Selga E, Noé V, Ciudad CJ. Biochemical Pharmacology 2007 Sep 8; Article in press) is the following:; While studying differentially expressed genes between sensitive and 10-5 M Methotrexate (MTX) resistant HT29 human colon cancer cells, we identified some members of the aldo-keto reductase (AKR) superfamily. The study was followed with the member AKR1C1 (EC 1.1.1.213), validating its increase in mRNA and protein levels in MTX resistant cells. The genomic content for AKR1C1 remained unchanged between sensitive and resistant cells, thereby excluding a mechanism of AKR1C1 gene amplification. Thus, we cloned the AKR1C1 human promoter and performed luciferase experiments that revealed a transcriptional regulation of the gene in the resistant cells. Computational studies showed a putative binding site for the transcription factor Sp1. The co-transfection of Sp1 or Sp3 with different constructs of AKR1C1 promoter deletions, including and excluding the proximal GC-box, demonstrated a key role for these factors in regulating AKR1C1 transcriptional activity. Gel-shift assays revealed an increase in Sp1 and Sp3 binding in resistant compared to sensitive cells, without differences in Sp1 protein levels. Dephosphorylation of the extracts coincided with a decrease in Sp1 binding, which is consistent with a process of regulation of Sp1 by phosphorylation. We also investigated the possible relationship between AKR1C1 expression and MTX action. Overexpression of AKR1C1 counteracted the S-phase accumulation of cells and apoptosis caused by MTX treatment. This suggests a role of AKR1C1 in cell proliferation. Finally, overexpression of AKR1C1 in MTX sensitive HT29 cells conferred resistance to the chemotherapeutic agent and silencing of AKR1C1 by means of iRNA technology sensitized the cells to MTX. Experiment Overall Design: Two cell lines are compared in the study, which are HT29 colon cancer cells sensitive to methotrexate and HT29 cells resistant to 10e-5M methotrexate. Six samples are provided, which correspond to triplicates of each cell line. The samples provided were subsequently normalyzed and analyzed using the specific software GeneSpring GX 7.3.1
2008-06-16 | E-GEOD-9412 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series:; GSE11440: Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCa on resistance to methotrexate in human HT29 colon cancer cells; GSE16066: Networking of differentially expressed genes in CaCo2 human colon cancer cells resistant to methotrexate; GSE16070: Networking of differentially expressed genes in human MCF7 breast cancer cells resistant to methotrexate; GSE16080: Networking of differentially expressed genes in human MDA-MB-468 breast cancer cells resistant to methotrexate; GSE16082: Networking of differentially expressed genes in human MIA PaCa2 pancreatic cancer cells resistant to methotrexate; GSE16085: Networking of differentially expressed genes in human K562 erythtoblastic leukemia cells resistant to methotrexate; GSE16089: Networking of differentially expressed genes in human Saos-2 osteosarcoma cells resistant to methotrexate Experiment Overall Design: Refer to individual Series
2009-09-11 | E-GEOD-16648 | biostudies-arrayexpress
Project description:The abstract of the associated publication (Selga E, Noé V, Ciudad CJ. Biochemical Pharmacology, 2008) is the following: While studying differentially expressed genes between sensitive and 10-5 M Methotrexate (MTX) resistant HT29 human colon cancer cells, we identified some members of the aldo-keto reductase (AKR) superfamily. The study was followed with the member AKR1C1 (EC 1.1.1.213), validating its increase in mRNA and protein levels in MTX resistant cells. The genomic content for AKR1C1 remained unchanged between sensitive and resistant cells, thereby excluding a mechanism of AKR1C1 gene amplification. Thus, we cloned the AKR1C1 human promoter and performed luciferase experiments that revealed a transcriptional regulation of the gene in the resistant cells. Computational studies showed a putative binding site for the transcription factor Sp1. The co-transfection of Sp1 or Sp3 with different constructs of AKR1C1 promoter deletions, including and excluding the proximal GC-box, demonstrated a key role for these factors in regulating AKR1C1 transcriptional activity. Gel-shift assays revealed an increase in Sp1 and Sp3 binding in resistant compared to sensitive cells, without differences in Sp1 protein levels. Dephosphorylation of the extracts coincided with a decrease in Sp1 binding, which is consistent with a process of regulation of Sp1 by phosphorylation. We also investigated the possible relationship between AKR1C1 expression and MTX action. Overexpression of AKR1C1 counteracted the S-phase accumulation of cells and apoptosis caused by MTX treatment. This suggests a role of AKR1C1 in cell proliferation. Finally, overexpression of AKR1C1 in MTX sensitive HT29 cells conferred resistance to the chemotherapeutic agent and silencing of AKR1C1 by means of iRNA technology sensitized the cells to MTX. Keywords: DHFR, Methotrexate, drug-resistance
2007-12-30 | GSE9412 | GEO
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61816 | biostudies-arrayexpress
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61620 | biostudies-arrayexpress
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression. Genome-wide profiling of gene expression in KY170R v. KY170 and TE13R v. TE13 using Illumine Human-6 V3 microarray indicated that over 900 genes were found to be remarkably differentiated. Among them, AKR1C3, an aldo-keto reductase existing at a low level in most human tissues, attracted our attention due to its significant expression in both radioresistant cells.
2014-09-27 | E-GEOD-61772 | biostudies-arrayexpress
Project description:Underexpression of miR-224 in methotrexate resistant human colon cancer cells
| PRJNA139061 | ENA
Project description:Genome-wide analysis of boswellic acids-mediated gene regulation. The hypothesis tested in the present study was that boswellic acids up-regulate some subset of genes in part thorough demethylation of those promotor regions. Results provide important information on boswellic acids-mediated anti-cancer effects in human colon cancer. Total RNA obtained from the human colorectal cancer SW48 cells treated with DMSO alone or acetyl-11-keto-?-boswellic acid (AKBA).
2012-12-01 | E-GEOD-32274 | biostudies-arrayexpress
Project description:Networking of differentially expressed genes in CaCo2 human colon cancer cells resistant to methotrexate
| PRJNA123093 | ENA
Project description:With the aim to elucidate the etiology of radioresistance, we explored the genetic alterations in non-radioresistant vs. resistant esophageal cancer cells acquired by long-term fractionated radiation. We found AKR1C3, an aldo-keto reductase expressed seldom in most human tissues, expressed higher in radioresistance-acquired cells. Suppression of AKR1C3 via RNAi or its chemical inhibitors restored the sensitivity of the acquired tumor cells and xenograft nude mice to ionizing radiation (IR). We also found the potential involvement of AKR1C3 in removal of cellular ROS and explain, at least partially, the acquired radioresistance by AKR1C3 overexpression.
2014-09-27 | GSE61772 | GEO