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  4. Identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation.
 
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Identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation.
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Identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation.pdf (1.8 MB)
Published version
Author(s)
Strath, Janet
Georgopoulos, Lindsay J
Kellam, Paul
Blair, G Eric
Type
Journal Article
Abstract
BACKGROUND: Cells transformed by human adenoviruses (Ad) exhibit differential capacities to induce tumours in immunocompetent rodents; for example, Ad12-transformed rodent cells are oncogenic whereas Ad5-transformed cells are not. The E1A gene determines oncogenic phenotype, is a transcriptional regulator and dysregulates host cell gene expression, a key factor in both cellular transformation and oncogenesis. To reveal differences in gene expression between cells transformed with oncogenic and non-oncogenic adenoviruses we have performed comparative analysis of transcript profiles with the aim of identifying candidate genes involved in the process of neoplastic transformation. RESULTS: Analysis of microarray data revealed that a total of 232 genes were differentially expressed in Ad12 E1- or Ad5 E1-transformed BRK cells compared to untransformed baby rat kidney (BRK) cells. Gene information was available for 193 transcripts and using gene ontology (GO) classifications and literature searches it was possible to assign known or suggested functions to 166 of these identified genes. A subset of differentially-expressed genes from the microarray was further examined by real-time PCR and Western blotting using BRK cells immortalised by Ad12 E1A or Ad5 E1A in addition to Ad12 E1- or Ad5 E1-transformed BRK cells. Up-regulation of RelA and significant dysregulation of collagen type I mRNA transcripts and proteins were found in Ad-transformed cells. CONCLUSION: These results suggest that a complex web of cellular pathways become altered in Ad-transformed cells and that Ad E1A is sufficient for the observed dysregulation. Further work will focus on investigating which splice variant of Ad E1A is responsible for the observed dysregulation at the pathway level, and the mechanisms of E1A-mediated transcriptional regulation.
Date Issued
2009-02-06
Date Acceptance
2009-02-06
Citation
BMC Genomics, 2009, 10
URI
http://hdl.handle.net/10044/1/61374
DOI
https://www.dx.doi.org/10.1186/1471-2164-10-67
ISSN
1471-2164
Publisher
BioMed Central
Journal / Book Title
BMC Genomics
Volume
10
Copyright Statement
© 2009 Strath et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
http://creativecommons.org/licenses/by/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/19200380
Subjects
Adenoviridae Infections
Adenoviruses, Human
Animals
Cell Line, Transformed
Cell Transformation, Viral
Gene Expression Regulation
Oligonucleotide Array Sequence Analysis
RNA
Rats
Rats, Wistar
Publication Status
Published online
Coverage Spatial
England
Article Number
67
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