Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Pancreatic Tumor vs Various Tissue Normals

ABSTRACT: Pancreatic Tumor samples from biopsy collected at different stages along with normal tissue samples from various organ sites including commercial normals arrayed on 2channel Agilent 60mer Oligo arrays (human v1 & v2), median normalized for cross comparison. Some normal samples temporarily removed to public due to Intelectual property conflict. Keywords: Pancreatic tumor comparison to normals for multimetric study Single channel array expression from two Agilent versions (V1:18k,V2: 22k) (i.e: GPL885,GPL887) combined based on matching probes, remove repeating control substituted with median values, final probe down to ~17k.

ORGANISM(S): Homo sapiens

SUBMITTER: Yoga Balagurunathan

PROVIDER: E-GEOD-11838 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer.

Balagurunathan Yoganand Y Morse David L DL Hostetter Galen G Shanmugam Vijayalakshmi V Stafford Phillip P Shack Sonsoles S Pearson John J Trissal Maria M Demeure Michael J MJ Von Hoff Daniel D DD Hruby Victor J VJ Gillies Robert J RJ Han Haiyong H

Molecular cancer therapeutics 20080902 9

Multimeric ligands are ligands that contain multiple binding domains that simultaneously target multiple cell-surface proteins. Due to cooperative binding, multimeric ligands can have high avidity for cells (tumor) expressing all targeting proteins and only show minimal binding to cells (normal tissues) expressing none or only some of the targets. Identifying combinations of targets that concurrently express in tumor cells but not in normal cells is a challenging task. Here, we describe a novel ...[more]

PMID: 18765825

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Project description:Signal recognition particles (SRPs) are important components in regulating intracellular protein transport and secretion, and tumors with high expression of Signal recognition particle 9 (SRP9) have tended to have poorer overall survival, although no reports have described the relationship between its localization and prognosis in pancreatic cancer. We conducted immunohistochemical staining for SRP9 for excised specimens from pancreatic cancer surgery cases without preoperative chemotherapy or radiotherapy performed. We found that in some cases SRP9 was preferentially expressed in the nucleus of the cancerous regions, which was hardly detected in other cases, suggesting SRP9 was transported to nucleus in the former cases. Therefore, the prognosis of patients with SRP9 nuclear translocation was compared by dividing them into two groups: those with a nuclear translocation rate of >50% and ≤50%. Patients with a nuclear translocation rate of >50% had significantly better recurrence-free survival compared with nuclear translocation rate of ≤50% group (p = 0.037). Subsequent in vitro experiments also showed that its nuclear translocation rate is reduced under amino acid deficient conditions. Further, to investigate the mechanism of SRP9 nuclear translocation, we studied in vitro by introducing the genes of SRP9 splicing variants (v1 and v2) and their deletion mutants lacking C-terminal regions into MiaPaCa pancreatic cancer cells. As a result, it was confirmed that both splicing variants showed nuclear translocation regardless of C-terminal deletions. Taking advantage of the fact that SRP9 is an RNA-binding protein, we next decided to sequence RNAs that bind to nuclear translocated v1 and v2 and evaluate their function in nuclear translocation. RNA Immunoprecipitation Sequencing of nuclear translocated v1 and v2 showed that pathways involved in cancer progression and protein translation were downregulated. The further study of nuclear translocation of SRP9 may open an avenue to optimization of precise evaluation and therapeutic control of pancreatic cancer.

Project description:This study was designed to identify changes in gene expression when corn was placed under various related stresses including being grown with a competing weed (canola) to the V4 or V8 stage, or when 40% shade cloth was present to the V4 or V8 stage, or under low nitrogen (no added nitrogen fertilizer), or under weed/shade free fertilized control conditions. In all 5 treatments and the control, samples were harvested at V8. Mechanisms underlying early season weed stress on crop growth are not well described. Corn vegetative growth and development, yield, and gene expression response to nitrogen (N), light (40% shade), and weed stresses were compared with the response of nonstressed plants. Vegetative parameters, including leaf area and biomass, were measured from V2 toV12 corn stages. Transcriptome (2008) or quantitative Polymerase Chain Reaction (q PCR) (2008/09) analyses examined differential gene expression in stressed versus nonstressed corn at V8. Vegetative parameters were impacted minimally by N stress although grain yield was 40% lower. Shade, present until V2, reduced biomass and leaf area > 50% at V2 and, at V12, recovering plants remained smaller than nonstressed plants. Grain yields of shade-stressed plants were similar to nonstressed controls, unless shade remained until V8. Growth and yield reductions due to weed stress in 2008 were observed when weeds remained until V6. In 2009, weed stress at V2 reduced vegetative growth, and weed stress until V4 or later reduced yield. Principle component analysis of differentially expressed genes indicated that shade and weed stress had more similar gene expression patterns to each other than to nonstressed or low N stressed tissues. Weed-stressed corn had 630 differentially expressed genes compared with the nonstressed control. Of these genes, 259 differed and 82 were shared with shade-stressed plants. Corn grown in N-stressed conditions shared 252 differentially expressed genes with weed-stressed plants. Ontologies associated with light/photosynthesis, energy conversion, and signaling were down-regulated in response to all three stresses. Although shade and weed stress clustered most tightly together, only three ontologies were shared by these stresses, O-methyltransferase activity (lignification processes), Poly U binding activity (post-transcriptional gene regulation), and stomatal movement. Based on both morphologic and genomic observations, results suggest that shade, N, and weed stresses to corn are regulated by both different and overlapping mechanisms. three biological replicates for each treatment and the control were collected and the resulting labeled cDNA was hybridized to the 46,000-element maize microarray chip developed by the University of Arizona using their protocol (International Microarray Workshop Handbook, 2009Gardiner et al. 2005). The hybridization scheme was a dual hybridization using a rolling circle balanced dye swap design. Thus we had thre biological replicates for each growth condition amd two technical replicates for each biological sample.

Dataset Information

Pancreatic Tumor vs Various Tissue Normals

Publications

Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer.

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