Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of normal and tumorigenic Rattus norvegicus cell lines grown under normal and arginine deprivation conditions

ABSTRACT: Goals of the Study:; 1. Assess the scope of arginine-responsive hepatic gene expression using in vitro rat models. 2. Compare normal and tumorigenic cells; 3. Identify potentially novel genes and pathways that may be subject to amino acid (arginine) regulation; Background: We previously reported that mRNA levels of the tumor associated glycoprotein amino acid transporter TA1/LAT1/ CD98 light chain arginine increase in normal hepatic cells under low arginine conditions while levels are constitutive and high in hepatic tumor cells. This suggested LAT1 amino acid response was associated with the normal hepatic phenotype and lost in carcinogenesis and may impact cell growth and survival in the tumor microenvironment. We sought to investigate how many and what types of genes are responsive to a change in arginine levels over 18 hrs using an in vitro model system. Experimental design:; Differential gene expression was determined by microarrays using samples from triplicates of normal and transformed cells subjected to 18 hour arginine-deprivation compared to controls

ORGANISM(S): Rattus norvegicus

SUBMITTER: Xianne Leong

PROVIDER: E-GEOD-2275 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis.

Leong Hwei Xian HX Simkevich Carl C Lesieur-Brooks Anne A Lau Bonnie W BW Fugere Celine C Sabo Edmond E Thompson Nancy L NL

Nutrition & metabolism 20060908

<h4>Background</h4>We have reported arginine-sensitive regulation of LAT1 amino acid transporter (SLC 7A5) in normal rodent hepatic cells with loss of arginine sensitivity and high level constitutive expression in tumor cells. We hypothesized that liver cell gene expression is highly sensitive to alterations in the amino acid microenvironment and that tumor cells may differ substantially in gene sets sensitive to amino acid availability. To assess the potential number and classes of hepatic gene ...[more]

PMID: 16961918

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Project description:Analysis of the response to arginine of the Escherichia coli K-12 transcriptome by microarray hybridization and real-time quantitative PCR provides a first coherent quantitative picture of the ArgR-mediated repression of arginine biosynthesis and uptake genes. Transcriptional repression was shown to be the major control mechanism of the biosynthetic genes, leaving only limited room for additional transcriptional or post-transcriptional regulations. The art genes coding for the specific arginine uptake system are subject to ArgR-mediated repression, ; with a strong repression of artJ, coding for the periplasmic binding protein of the system. The hisJQMP genes of the histidine transporter (part of the LAO uptake system) were discovered to be a part of the arginine regulon. Analysis of their control region with reporter gene fusions and electrophoretic mobility shift in the presence of pure ArgR repressor showed the involvement in repression of the ArgR protein and of an ARG box 120 bp upstream of hisJ. No repression of the genes of the AO uptake system was observed. Finally, comparing the time course of arginine repression of gene transcription with the evolution of the specific ; activities of the cognate enzymes showed that while full genetic repression was achieved two minutes after arginine addition, enzyme concentrations were diluted at the rate of cell ; division. This emphasizes the importance of the feedback-inhibition of the first enzymatic ; step of the pathway in controlling the metabolic flow through the biosynthesis in the period following the onset of repression. Experiment Overall Design: 3 groups of 3 replicate samples were analyzed: Experiment Overall Design: (1) Wild type on minimal medium (strain P4X, slides 1753, 1765, 1989), this created a reference condition Experiment Overall Design: (2) Wild type grown in the presence of arginine (strain P4X plus 100Âµg/ml of arginine, slides 1754, 1766, 1990), this gave a list of all the genes repressed by the system: ArgR+arginine Experiment Overall Design: (3) Mutant where no active repressor is present; grown in the presence of arginine (strain P4XB2 (argR-) plus 100Âµg/ml arginine, slides 1992, 1993, 1994). This condition told us which genes are indeed regulated by the system: ArgR+arginine. Those genes are in this case derepressed.

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Dataset Information

Transcription profiling of normal and tumorigenic Rattus norvegicus cell lines grown under normal and arginine deprivation conditions

Publications

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis.

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