Genomic Organization of Two Novel Genes on Human Xq28: Compact Head to Head Arrangement ofIDHγ andTRAPδ Is Conserved in Rat and Mouse

Brenner, Volker; Nyakatura, Gerald; Rosenthal, André; Platzer, Matthias

doi:10.1006/geno.1997.4822

Cited by 30 publications

(31 citation statements)

References 23 publications

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“…FAM46C has been suggested to be involved in the regulation of protein translation, but its exact function is unknown (36). Signal sequence receptor delta (SSR4) encodes one subunit of the translocon-associated protein complex involved in the transport of proteins across the endoplasmic reticulum membrane (37).…”

Section: Baseline Characteristics Of the Uppsala Cohortmentioning

confidence: 99%

Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

Botling

Edlund

Lohr

et al. 2013

Clinical Cancer Research

285

244

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Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n ¼ 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.

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Section: Baseline Characteristics Of the Uppsala Cohortmentioning

confidence: 99%

Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

Botling

Edlund

Lohr

et al. 2013

Clinical Cancer Research

285

244

View full text Add to dashboard Cite

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“…To test whether mitochondria are more abundant in the surface epithelium, we performed immunohistochemical staining for the g subunit of the NAD 1 -dependent isocitrate dehydrogenase complex (isocitrate dehydrogenase 3-g, IDH3G). This enzyme is a ubiquitously expressed mitochondrial matrix protein in mammals (22,23), and catalyzes the oxidative decarboxylation of isocitrate. This reaction is an irreversible and energy-yielding step in the Krebs cycle.…”

Section: Mitochondrial Distribution Is Highly Skewed Toward Surface Ementioning

confidence: 99%

Differential Gene Expression in Human Conducting Airway Surface Epithelia and Submucosal Glands

Fischer¹,

Goss²,

Scheetz³

et al. 2009

Am J Respir Cell Mol Biol

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Human conducting airways contain two anatomically distinct epithelial cell compartments: surface epithelium and submucosal glands (SMG). Surface epithelial cells interface directly with the environment and function in pathogen detection, fluid and electrolyte transport, and mucus elevation. SMG secrete antimicrobial molecules and most of the airway surface fluid. Despite the unique functional roles of surface epithelia and SMG, little is known about the differences in gene expression and cellular metabolism that orchestrate the specialized functions of these epithelial compartments. To approach this problem, we performed large-scale transcript profiling using epithelial cell samples obtained by laser capture microdissection (LCM) of human bronchus specimens. We found that SMG expressed high levels of many transcripts encoding known or putative innate immune factors, including lactoferrin, zinc a-2 glycoprotein, and proline-rich protein 4. By contrast, surface epithelial cells expressed high levels of genes involved in basic nutrient catabolism, xenobiotic clearance, and ciliated structure assembly. Selected confirmation of differentially expressed genes in surface and SMG epithelia demonstrated the predictive power of this approach in identifying genes with localized tissue expression. To characterize metabolic differences between surface epithelial cells and SMG, immunostaining for a mitochondrial marker (isocitrate dehydrogenase) was performed. Because greater staining was observed in the surface compartment, we predict that these cells use significantly more energy than SMG cells. This study illustrates the power of LCM in defining the roles of specific anatomic features in airway biology and may be useful in examining how disease states alter transcriptional programs in the conducting airways.Keywords: airway epithelia; microarray; submucosal glandThe airways maintain a dynamic interface with the environment. The continuity of the airway epithelium serves as a physical barrier to inhaled pathogens, while the secreted protein and peptide products of the tissue, in concert with ciliary function, support mucociliary clearance and host defense. The epithelium of the intrapulmonary airways contributes to pulmonary innate immunity as a first responder and as an important site of signal amplification. Through a variety of receptor systems, the surface epithelial cells sense and respond to inhaled chemical, microbial, thermal, and particulate stimuli to maintain health. Perturbation of the function of this tissue is involved in the pathogenesis of several diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF).The epithelial tissue of the conducting airways includes many specialized cell types and the spatial division of functions. Two anatomically distinct conducting airway compartments are the airway surface epithelium and submucosal glands (SMG). The surface epithelium of the cartilaginous conducting airways is composed of ciliated, nonciliated, goblet, and basal cell ty...

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“…Ten other EBV-induced genes are constituents of metabolic pathways, including protein biosynthesis and degradation, PCBD/6-pyruvoly-tetrahydropterin synthase, vacuolar ATPase subunit H, phosphoglycerate kinase 1 (PGK1), enolase 2, DNase I-like elongation and initiation factor 4B, ribosomal protein S8, signal sequence receptor 4, cystatin B, and cathepsin C (11,17,22,31,39,67,75,78,79,86,93,111,122). Up-regulation of these RNAs may enhance the ability of latency III-infected cells to rapidly alter location, metabolism, or proliferation.…”

Section: Vol 76 2002 Ebv Effects On Cell Mrnas 10431mentioning

confidence: 99%

Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

Carter

Cahir-McFarland

Kieff

2002

J Virol

134

108

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In primary Epstein-Barr virus (EBV) infection, a substantial fraction of peripheral blood B lymphocytes are latently infected and express virus-encoded proteins that are capable of causing continuous B-cell proliferation. The EBV-encoded proteins engender an unusually vigorous and large T-cell immune response which eliminates most of the virus-infected cells. In severely T-cell immune-compromised or otherwise susceptible people, the EBV-infected B lymphocytes can malignantly proliferate (reviewed in reference 90).The EBV gene products that are expressed in primary lymphocyte infection and that stimulate cell proliferation include six nuclear antigen proteins (EBNAs), two latent infection integral membrane proteins (LMPs), two small RNAs (EBERs), and BamA rightward transcripts (BARTs) of uncertain function (reviewed in reference 59). This complex infection, termed latency III, is characteristic of EBV gene expression in EBV-transformed lymphoblastoid cell lines (LCLs) and many lymphoproliferations that occur in immune-deficient humans (23, 95).Many of the EBV effects on cell growth and survival are likely to be mediated by EBV-induced changes in cell gene transcription. Five of the EBNAs can alter cell gene transcription through their direct or indirect interaction with the cellular DNA sequence-specific transcription factors RBP-j/CBF1, PU.1, and AUF1 (35,42,52,53,65,72,91,113,119,123). Furthermore, EBV LMP1 is similar to a constitutively activated CD40 receptor and activates NF-B, Jun/Fos, and AP1 cellular transcription factors (27,28,30,33,36,40,45,50,60,66,81,83). Moreover, EBV LMP2 is similar to a constitutively activated B-cell antigen receptor (BCR) in causing a stable small increase in BCR tyrosine kinase signaling and in desensitizing the cell to BCR-type signal transduction (12, 80). Four of the EBNAs that interact with cellular transcription factors and LMP1 are critical for EBV effects on cell growth and survival, while EBNA3B, LMP2, EBERs, and BARTs are not (19,37,49,56,68,73,76,92,102,108,109).In the experiments reported here, cDNA arrays were used to investigate the effects of EBV latency III infection on cell gene transcription. cDNA arrays are particularly useful in characterizing changes in expression of large numbers of cellular genes (3,4,48,51,57,74,97,100). We compared gene expression in BL41, an EBV-negative Burkitt's lymphoma (BL) cell line, with gene expression in two latency III-expressing cell lines-BL41 infected in vitro with EBV (BL41EBV) and an LCL (IB4) (18,62). In contrast to a comparison of LCLs with resting B lymphocytes, which would identify a large number of cell genes whose expression is up-regulated at various points in the cell cycle, comparison with a non-EBV-infected BL cell line will identify genes that are specifically up-regulated by EBV latency III proteins. However, EBV-regulated genes whose transcription is inherent to the BL phenotype, such as c-myc, may escape detection. MATERIALS AND METHODS Cell

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Genomic Organization of Two Novel Genes on Human Xq28: Compact Head to Head Arrangement ofIDHγ andTRAPδ Is Conserved in Rat and Mouse

Cited by 30 publications

References 23 publications

Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

Differential Gene Expression in Human Conducting Airway Surface Epithelia and Submucosal Glands

Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

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