Am J Cancer Res 2012;2(6):699-713
Review Article
Transcriptional profiling reveals elevated Sox2 in DNA
polymerase ß null mouse embryonic fibroblasts
Jianfeng Li, Soumya Luthra, Xiao-Hong Wang, Uma R Chandran, Robert W Sobol
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh,
PA 15213, USA; University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA;
Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213,
USA
Received Octorber 18, 2012; Accepted November 2, 2012; Epub November 20, 2012; Published November 30,
2012
Abstract: There are over 150 human proteins that have been categorized as bona fide DNA repair proteins. These
DNA repair proteins maintain the integrity of the genome, reducing the onset of cancer, disease and aging phenotypes.
Variations in expression and/or function would therefore impact genome integrity as well as the cellular
response to genotoxins. Global gene expression analysis is an effective approach to uncover defects in DNA repair
gene expression and to discover cellular and/or organismal effects brought about by external stimuli such as environmental
genotoxicants, chemotherapeutic regimens, viral infections as well as developmental and age-related
stimuli. Given the significance of genome stability in cell survival and response to stimuli, we have hypothesized that
cells may undergo transcriptional re-programming to accommodate defects in basal DNA repair capacity to promote
survival. As a test of this hypothesis, we have compared the transcriptome in three DNA polymerase ß knockout
(Polß-KO) mouse embryonic fibroblasts (MEFs) and the corresponding wild-type (WT) littermate control cell lines.
Each Polß-KO cell line was found to have a range of genes up-regulated, when compared to its WT littermate control
cell line. Interestingly, six (6) genes were commonly up regulated in all three Polß-KO cell lines, including Sox2, one
of several genes associated with the induction of pluripotent stem cells. Herein, we present these findings and suggest
that loss of DNA repair and the induction of cellular transcriptional re-programming may, in part, contribute to
tumor formation and the cellular response to external stimuli. (ajcr0000152).
Keywords: DNA polymerase ß, mouse embryonic fibroblast, Sox2, gene expression profiling, transcriptional reprogramming
Address all correspondence to:
Dr. Robert W Sobol
Hillman Cancer Center
University of Pittsburgh Cancer Institute
Research Pavilion, Suite 2.6a, 5117 Centre Avenue
Pittsburgh, Pennsylvania 15213-1863.
Phone: 412-623-7764
E-mail: rws9@pitt.edu
Review Article
Transcriptional profiling reveals elevated Sox2 in DNA
polymerase ß null mouse embryonic fibroblasts
Jianfeng Li, Soumya Luthra, Xiao-Hong Wang, Uma R Chandran, Robert W Sobol
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh,
PA 15213, USA; University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA;
Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;
Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213,
USA
Received Octorber 18, 2012; Accepted November 2, 2012; Epub November 20, 2012; Published November 30,
2012
Abstract: There are over 150 human proteins that have been categorized as bona fide DNA repair proteins. These
DNA repair proteins maintain the integrity of the genome, reducing the onset of cancer, disease and aging phenotypes.
Variations in expression and/or function would therefore impact genome integrity as well as the cellular
response to genotoxins. Global gene expression analysis is an effective approach to uncover defects in DNA repair
gene expression and to discover cellular and/or organismal effects brought about by external stimuli such as environmental
genotoxicants, chemotherapeutic regimens, viral infections as well as developmental and age-related
stimuli. Given the significance of genome stability in cell survival and response to stimuli, we have hypothesized that
cells may undergo transcriptional re-programming to accommodate defects in basal DNA repair capacity to promote
survival. As a test of this hypothesis, we have compared the transcriptome in three DNA polymerase ß knockout
(Polß-KO) mouse embryonic fibroblasts (MEFs) and the corresponding wild-type (WT) littermate control cell lines.
Each Polß-KO cell line was found to have a range of genes up-regulated, when compared to its WT littermate control
cell line. Interestingly, six (6) genes were commonly up regulated in all three Polß-KO cell lines, including Sox2, one
of several genes associated with the induction of pluripotent stem cells. Herein, we present these findings and suggest
that loss of DNA repair and the induction of cellular transcriptional re-programming may, in part, contribute to
tumor formation and the cellular response to external stimuli. (ajcr0000152).
Keywords: DNA polymerase ß, mouse embryonic fibroblast, Sox2, gene expression profiling, transcriptional reprogramming
Address all correspondence to:
Dr. Robert W Sobol
Hillman Cancer Center
University of Pittsburgh Cancer Institute
Research Pavilion, Suite 2.6a, 5117 Centre Avenue
Pittsburgh, Pennsylvania 15213-1863.
Phone: 412-623-7764
E-mail: rws9@pitt.edu
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American Journal of Cancer Research
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