Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA117953 | ENA |
REPOSITORIES: ENA
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Project description:Previous reports demonstrate that the α2-integrin (α2) mediates pancreatic ductal adenocarcinoma (PDAC) cell interaction with collagens. We found that untransformed pancreatic ductal epithelial cells and well-differentiated PDAC cells use α2 exclusively to adhere and migrate on collagenI. In contrast, poorly-differentiated PT45P1 and MIAPaCa2 cells demonstrate reduced reliance on, or complete loss of α2, respectively. Further, well-differentiated PDAC lines exhibit reduced in vitro invasion compared to poorly-differentiated lines, and α2-blockade suppressed invasion of well-differentiated lines exclusively. Based on these data and the demonstrated role of α2 in maintaining tissue architecture in other organs, we hypothesized that α2 may actually suppress the malignant phenotype in PDAC. Accordingly, stable ectopic expression of α2 in MIAPaCa2 cells (MP2-α2) retarded in vitro invasion. MP2-α2 cells maintained on collagenI were more invasion-retarded than MP2-α2 cells maintained in standard tissue culture, and demonstrated higher α2β1 expression that was reflected in faster and more complete adhesion/migration on collagenI. Affymetrix gene expression profiling of α2-expressing and mock-transfected cells revealed that kallikrein-related peptidases (KLK)-5, 6 and 7 were specifically upregulated by α2. Accordingly, well-differentiated PDAC lines express KLK-5, 6 and 7 and KLK blockade increased invasion as well as collagenI-migration in KLK-positive lines. Importantly, an α2 cytoplasmic deletion mutant promoted KLK expression and retarded invasion, while an α9α2 chimera retarded invasion less efficiently, and did not impact KLK expression. These data demonstrate for the first time that the α2-ectodomain and KLKâ??s coordinately regulate a less invasive phenotype in PDAC cells. Experiment Overall Design: Affymetrix global gene arrays were used to analyse differences in gene expression patterns in MIAPaCa2 cells stably reexpressing the alpha2 integrin, a cytoplasmic deletion of the alpha2 integrin (dCYTO) or an alpha9 ectodomain and transmembrane domain/alpha2 cytoplasmic domain chimera, versus vector-only mock controls. RNA was harvested from cells passaged identically and maitained under standard tissue culture conditions or on collagenI- or tenascin FNIII-coated plates.. Experiment Overall Design: Genetic manipulation (stable transgene expression)
2009-10-03 | E-GEOD-18277 | biostudies-arrayexpress
Project description:CRISPR-cas9 technology was used to knock out alpha2 integrin in DU145 cells. To create two cell lines that could be compared to each other in an appropriate manner, these cells were transfected either with alpha2 integrin cDNA or empty vector. The objective of the study was to find potential alpha2 integrin regulated genes when the cells were grown as spheroids.
2018-08-02 | GSE111507 | GEO
Project description:To test whether nuclear importin alpha2 can regulate transcription, we sought to examine gene expression changes in cells with nuclear accumulation of importin alpha2 by performing microarray analysis. We designed an experiment in which EGFP-fused full-length importin alpha2 was transfected into HeLa cells. To exclude the possibility that exogenous, full-length importin alpha2 protein enhances nuclear transport of karyophilic proteins such as transcription factors and thereby directly influences gene expression, a mutant of importin alpha2 which is mutated in the C-terminal CAS-binding domain was also transfected, so that it is never recycled to the cytoplasm and shows complete nuclear localization. We undertook to investigate whether there were changes in gene expression common to cells expressing the full-length importin alpha2 and the C-terminal mutant (C-mutant) isoform. EGFP vs. EGFP-importin alpha2 full length, or EGFP vs EGFP-importin alpha2 CAS-binding mutant. One replicate each. EGFP-expressing cells are used as a control.
2010-11-24 | E-GEOD-25303 | biostudies-arrayexpress
Project description:Transcriptome profiling of Caki2 cells re-expressing Polybromo-1 (PBRM1)
| PRJNA306616 | ENA
Project description:To test whether nuclear importin alpha2 can regulate transcription, we sought to examine gene expression changes in cells with nuclear accumulation of importin alpha2 by performing microarray analysis. We designed an experiment in which EGFP-fused full-length importin alpha2 was transfected into HeLa cells. To exclude the possibility that exogenous, full-length importin alpha2 protein enhances nuclear transport of karyophilic proteins such as transcription factors and thereby directly influences gene expression, a mutant of importin alpha2 which is mutated in the C-terminal CAS-binding domain was also transfected, so that it is never recycled to the cytoplasm and shows complete nuclear localization. We undertook to investigate whether there were changes in gene expression common to cells expressing the full-length importin alpha2 and the C-terminal mutant (C-mutant) isoform.
2010-11-24 | GSE25303 | GEO
Project description:Transcriptional profiling comparing MiaPaCa2 pancreatic cancer cells transfected with S100PBP siRNA to MiaPaCa2 cells transfected with non-targeting control siRNA
| PRJNA155967 | ENA
Project description:Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump alpha2-Na/K ATPase represent a key genetic cause of familial hemiplegic migraine, but the mechanisms by which alpha2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we unexpectedly find that mice in which alpha2-Na/K ATPase is conditionally deleted in astrocytes display episodic transient motor paralysis. Functional neuroimaging reveals that conditional knockout of alpha2-Na/K ATPase triggers spontaneous cortical spreading depression events that are associated with low voltage activity events upon EEG monitoring, which in turn correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that loss of alpha2-Na/K ATPase alters metabolic gene expression in astrocytes in vivo with consequent elevation of serine and glycine in the brain. Strikingly, feeding alpha2-Na/K ATPase knockout mice a serine- and glycine-free diet reverses the phenotype of transient motor impairment. Together, our findings define a novel metabolic mechanism regulated by astrocytic alpha2-Na/K ATPase that triggers episodic transient motor paralysis in mice, laying the foundation for potential new treatment strategies for patients with familial hemiplegic migraine.
2020-10-20 | GSE145102 | GEO
Project description:Previous reports demonstrate that the α2-integrin (α2) mediates pancreatic ductal adenocarcinoma (PDAC) cell interaction with collagens. We found that untransformed pancreatic ductal epithelial cells and well-differentiated PDAC cells use α2 exclusively to adhere and migrate on collagenI. In contrast, poorly-differentiated PT45P1 and MIAPaCa2 cells demonstrate reduced reliance on, or complete loss of α2, respectively. Further, well-differentiated PDAC lines exhibit reduced in vitro invasion compared to poorly-differentiated lines, and α2-blockade suppressed invasion of well-differentiated lines exclusively. Based on these data and the demonstrated role of α2 in maintaining tissue architecture in other organs, we hypothesized that α2 may actually suppress the malignant phenotype in PDAC. Accordingly, stable ectopic expression of α2 in MIAPaCa2 cells (MP2-α2) retarded in vitro invasion. MP2-α2 cells maintained on collagenI were more invasion-retarded than MP2-α2 cells maintained in standard tissue culture, and demonstrated higher α2β1 expression that was reflected in faster and more complete adhesion/migration on collagenI. Affymetrix gene expression profiling of α2-expressing and mock-transfected cells revealed that kallikrein-related peptidases (KLK)-5, 6 and 7 were specifically upregulated by α2. Accordingly, well-differentiated PDAC lines express KLK-5, 6 and 7 and KLK blockade increased invasion as well as collagenI-migration in KLK-positive lines. Importantly, an α2 cytoplasmic deletion mutant promoted KLK expression and retarded invasion, while an α9α2 chimera retarded invasion less efficiently, and did not impact KLK expression. These data demonstrate for the first time that the α2-ectodomain and KLK’s coordinately regulate a less invasive phenotype in PDAC cells.
2009-09-26 | GSE18277 | GEO
Project description:Strain background is BMA64 with RNT1 gene deleted with the TRP marker Media is SD -Trp (synthetic dextrose minimal media missing tryptophan) Cells were grown until midlog and harvested at OD600=0.4; MAS5 (Statistical Algorithm) Scaling:All Probe Sets Target Signal 500;Normalization:All Probe Sets; Alpha1=0.04; Alpha2=0.06; Tau=0.015,Strain background is BMA64 with plasmid expressing TRP marker Media is SD -Trp (synthetic dextrose minimal media missing tryptophan) Cells were grown until midlog and harvested at OD600=0.4,; MAS5 (Statistical Algorithm) Scaling:All Probe Sets Target Signal 500;Normalization:All Probe Sets; Alpha1=0.04; Alpha2=0.06; Tau=0.015
2007-07-07 | E-GEOD-2683 | biostudies-arrayexpress