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Results for “transcriptomic”

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At least 1,477 records · Page 82Linked to original sources
PubMed2003

Mismatch repair-dependent transcriptome changes in human cells treated with the methylating agent N-methyl-n'-nitro-N-nitrosoguanidine.

DNA mismatch repair (MMR) plays a key role in the cytotoxic response of human cells to methylating agents, however, the cascade of events leading to cell cycle arrest and cell death has yet to be characterized. We studied the role of MMR in the transcriptional response to DNA methylation damage in two human cellular models: (a). the lymphoblastoid cell line TK6 and its derivative MT1, which is mutated in the MMR gene hMSH6; and (b). the epithelial cell line 293T Lalpha in which the expression of the MMR gene hMLH1 can be tightly regulated and p53 is inactivated. Upon N-methyl-N'-nitro-N-nitrosoguanidine treatment, only cells with functional MMR were killed, but the type of cytotoxic response differed. In TK6 cells, S-phase arrest and apoptosis were accompanied by a dramatic change in gene expression, notably, an up-regulation of several genes encoding growth inhibitors and proapoptotic factors both p53 dependent and independent. In contrast, the MMR-dependent transcriptional response in 293T Lalpha cells was substantially less pronounced than in TK6 cells, despite an efficient induction of a G(2)-M checkpoint and nonapoptotic cell death. Thus, we demonstrate that in human cells of different origin, MMR-mediated killing by methylating agents occurs through different pathways and regardless of the p53 status. Moreover, once DNA methylation damage has been processed by the MMR system, tumor cells might be committed to die, although one or more of their signaling pathways are impaired.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Analysis of the root nodule-enhanced transcriptome in soybean.

For high throughput screening of root nodule-enhanced genes, cDNA libraries specific for three different developmental stages of soybean root nodules were constructed after inoculation with Bradyrhizobium japonicum USDA110. 5,469 cDNA clones were sequenced and grouped into 2,511 non-redundant (nr) ESTs consisting of 769 contigs and 1,742 singletons. Using similarity searches against several public databases we constructed a functional classification of the ESTs into root nodule-specific nodulin genes, stress-responsive genes and genes related to carbon and nitrogen metabolism. We also constructed a cDNA microarray with 382 selected clones that appeared to be up-regulated in the root nodule. Using the microarray we compared the transcript levels of uninfected roots and root nodules from four developmental stages. We identified 81 genes that were differentially expressed, and grouped them into seven clusters according to the similarity of their expression profiles, using a hierarchical clustering algorithm. Clusters 1, 2, 3, and 6, comprised of 58 genes, showed root nodule-enhanced expression. The information from this study will be used to analyze the roles of root nodule-specific genes and signaling pathways during root nodule development.

Databases, Nucleic Acid↗
PubMedDate not supplied

Transcriptome analysis of different multidrug-resistant gastric carcinoma cells.

Multidrug resistance (MDR) of human cancers is the major cause of failure of chemotherapy. To better understand the molecular events associated with the development of different types of MDR, two different multidrug-resistant gastric carcinoma cell lines, the MDR1/P-glycoprotein-expressing cell line EPG85-257RDB and the MDR1/P-glycoprotein-negative cell variant EPG85-257RNOV, as well as the corresponding drug-sensitive parental cell line EPG85-257P, were used for analyses of the mRNA expression profiles by cDNA array hybridization. Of more than 12,000 genes spotted on the arrays, 156 genes were detected as being significantly regulated in the cell line EPG85-257RDB in comparison to the non-resistant cell variant, and 61 genes were found to be differentially expressed in the cell line EPG85-257RNOV Seventeen genes showed a differential expression level in both multidrug-resistant gastric carcinoma variants. The impact of these alterations in gene expression levels in different multidrug-resistant gastric carcinoma cell variants is discussed.

Cell Line, Tumor↗
PubMed2005

Collection of soluble variants of membrane proteins for transcriptomics and proteomics.

The existence of a soluble splice variant for a gene encoding a transmembrane protein suggests that this gene plays a role in intercellular signalling, particularly in immunological processes. Also, the absence of a splice variant of a reported soluble variant suggests exclusive control of the solubilisation by proteolytic cleavage. Soluble splice variants of membrane proteins may also be interesting targets for crystallisation as their structure may be expected to preserve, at least partially, their function as integral membrane proteins, whose structures are most difficult to determine. This paper presents a dataset derived from the literature in an attempt to collect all reported soluble variants of membrane proteins, be they splice variants or shedded. A list of soluble variants is derived in silico from Ensembl. These are checked on their presence in multiple organisms and their number of membranespanning regions is inspected. The findings then are confirmed by a comparison with identified proteins of a recent global proteomics study of human blood plasma. Finally, a tool to determine novel soluble variants by proteomics is provided.

Animals↗
PubMed2005

Identifying genes with differential expression in gemcitabine-resistant pancreatic cancer cells using comprehensive transcriptome analysis.

Pancreatic cancer is often unresectable at diagnosis, and chemotherapy using gemcitabine is now the standard treatment for advanced pancreatic cancer. However, acquired resistance to gemcitabine resulting in therapeutic failure is often encountered. Therefore, we sought to identify genes that determine gemcitabine resistance by evaluating the relationship between gene expression profiles and gemcitabine sensitivity to provide molecular targets for overcoming gemcitabine resistance. First, the gemcitabine concentration needed for 50% growth inhibition was examined in six pancreatic cancer cell lines. By exposing MIA PaCa-2 cells to long-term gemcitabine, we established gemcitabine-resistant cells. The gene expression profiles of the six pancreatic cancer cell lines and gemcitabine-resistant cells were determined using cDNA microarray analysis. By comparing the results, 30 genes were identified as differentially expressed genes correlated with gemcitabine sensitivity. Differentially expressed genes in the parental cell lines were also examined, and six overlapping genes were identified as genes correlated with gemcitabine sensitivity in both assays. Of these genes, the down-regulated expression of TNFSF6 protein, also known as Fas ligand, was confirmed in the gemcitabine-resistant cell line. These results should provide therapeutic molecular targets for overcoming gemcitabine resistance.

Antimetabolites, Antineoplastic↗
PubMed2005

Integrating genomics and transcriptomics with geo-ethnicity and the environment for the resolution of complex cardiovascular diseases.

One of the crucial steps on the way to individualized medicine to treat cardiovascular disease (CVD) is to better understand the identities, roles, extent and at least the major patterns of interaction between influential genomic and environmental factors. It is clear that such a bold goal can hardly be achieved without a major upgrade of our conceptualization of the phenomena studied, taking advantage of recent developments of novel technological and computational tools. Firstly, the search for the genomic components of the most common multifactorial CVDs is no longer restricted to protein-coding genes; truly genome-wide investigations should replace them in both humans and animal models. Secondly, the 'environment' has also undergone semantic expansion, incorporating such remote constituents as developmental plasticity and epigenetics on one side, and socioeconomic status on the other. To elucidate and analyze the resulting complex picture, appropriate statistical models and approaches need to be designed to tackle issues such as population stratification and admixture, multiple testing, and multidimensionality reduction in models involving multiple genes and environmental factors. Eventually, an integrated platform bringing together all of the above will probably be necessary to secure relevant information specific to a particular combination of conditions and settings (age, geo-ethnicity and exposure), which may perhaps become visible only after a step back, through systems (network) biology.

Animals↗
PubMed2006

Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL) are derived from different cell types, namely T cells and B cells, respectively. However, both lymphomas share a similar cytological and immunohistochemical tumor cell phenotype with little resemblance to their cells of origin. DESIGN AND METHODS: In this study, the transcriptional profiles of ALCL cell lines, primary ALCL tumor cells from peripheral blood and HL cell lines were compared to each other and to normal B-cell subsets, B non-Hodgkin's lymphomas (NHL) and B NHL- and Epstein-Barr virus (EBV)-transformed B-cell lines in order to establish their relationship at the transcriptional level and to identify genes with possible pathobiological impact. Expression of some of the genes identified was confirmed in microdissected primary tumor cells by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: HL samples clustered separately from ALCL samples, but HL and ALCL were found to be more closely related to each other than to any normal or malignant B-cell sample in the dataset. Their relationship was determined to a large extent, but not exclusively, by lack of expression of B-cell antigens and by the over-expression of mRNA encoding activation markers and structural proteins. Apart from established differences between HL and ALCL, further genes of interest could be identified that distinguish both entities from each other and from the other samples. The differential expression of PRAME, DDR2, SOCS3 and CEBPD in HL and ALCL was confirmed in primary tumor tissue by immunohistochemistry and/or RT-PCR. INTERPRETATION AND CONCLUSIONS: At a transcriptional level HL is more closely related to Alk+ ALCL than to the B-NHL or B-cell samples investigated, although it is a B-cell derived lymphoma. The newly identified genes discriminating HL and ALCL may be pathobiologically important and may serve as possible therapeutic targets.

Adult↗
PubMed2006

Transcriptome characterization of human mammary cell lines expressing different levels of ERBB2 by serial analysis of gene expression.

Over-expression of ERBB2, a member of the family of transmembrane receptor tyrosine kinases, occurs in 15-30% of primary breast tumors and is associated with poor prognosis and chemoresistance to a variety of anticancer drugs. In this study, aiming to identify differentially-expressed genes involved in erbB2-mediated transformation of the breast, we generated SAGE libraries from two human mammary cell lines, derived from normal luminal cells, expressing different levels of erbB2. The parental cell line HB4a expresses basal levels and the C5.2 expresses high levels of erbB2. A total of 161,632 tags was generated by sequencing, 81,684 from HB4a cells (30,854 unique tags) and 79,948 from C5.2 cells (30,568 unique tags). The comparison between the HB4a and C5.2 libraries revealed 334 distinct transcripts more expressed in HB4a cells and 328 distinct transcripts more expressed in C5.2 cells. The expression pattern of some of these transcripts was further validated by RT-PCR. The C5.2 cell line, which over-express ERBB2, showed in comparison to HB4a cells a higher percentage of genes involved in transport, RNA processing, apoptosis and protein folding. A higher percentage of the genes more expressed in HB4a cells compared to C5.2 were found to be involved in signal transduction and cytoskeleton organization. The use of SAGE analysis allowed us to identify a significant number of genes implicated in different cellular pathways up- or down-regulated in the presence of ERBB2 over-expression, including genes not previously implicated in breast cancer that could be considered as potential candidate markers for prognosis and therapy.

Breast↗
PubMed2026

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Studying brain gene expression in Alzheimer's Disease (AD) remains difficult as postmortem brain is difficult to access, cannot be used to guide donor treatment, may be confounded by environmental factors before and after death, and is difficult to link to early AD states or disease progression. To circumvent these limitations, several studies have tested blood transcriptome biomarkers for AD. However, gene-expression levels in the blood have limited correlation with those in the brain. To evaluate the potential of monitoring Alzheimer's progression with peripheral data, we used transcriptome-imputation to identify brain-region-specific AD-associated gene-expression differences in cohorts with blood-based transcriptome data. This approach provides a high-resolution image of AD-associated molecular differences in the brains of individuals actively living with disease. We analyzed eight AD studies (777 AD cases, 779 cognitively unimpaired controls), imputing transcriptomes in 10 brain regions via the Brain Gene Expression and Network Imputation Engine (BrainGENIE). Hundreds of differentially expressed genes (DEGs) associated with AD were identified in nine brain regions, with anterior cingulate cortex and amygdala showing the most differential expression. AD-associated genes were enriched in pathways such as proteostasis, mitochondrial dysfunction, and immune activation. We observed significant yet moderate concordance between imputed AD-associated changes and those directly measured in the dorsolateral prefrontal cortex and cerebellum. These transcriptomic changes can guide future in vitro studies focused on pathogenesis or be targets of novel therapeutic development. In conclusion, we demonstrated the scope and utility of brain expression imputation from the peripheral transcriptome, laying the groundwork for biomarker discovery and prospective AD studies.

Alzheimer Disease↗