Comparative Transcriptome Profiling of an SV40-Transformed Human Fibroblast (MRC5CVI) and Its Untransformed Counterpart (MRC-5) in Response to UVB Irradiation

Simian virus 40 (SV40) transforms cells through the suppression of tumor-suppressive responses by large T and small t antigens; studies on the effects of these two oncoproteins have greatly improved our knowledge of tumorigenesis. Large T antigen promotes cellular transformation by binding and inactivating p53 and pRb tumor suppressor proteins. Previous studies have shown that not all of the tumor-suppressive responses were inactivated in SV40-transformed cells; however, the underlying cause is not fully studied. In this study, we investigated the UVB-responsive transcriptome of an SV40-transformed fibroblast (MRC5CVI) and that of its untransformed counterpart (MRC-5). We found that, in response to UVB irradiation, MRC-5 and MRC5CVI commonly up-regulated the expression of oxidative phosphorylation genes. MRC-5 up-regulated the expressions of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes, but MRC5CVI did not. Further cell death assays indicated that MRC5CVI was more sensitive than MRC-5 to UVB-induced cell death with increased caspase-3 activation; combining with the transcriptomic results suggested that MRC5CVI may undergo UVB-induced cell death through mechanisms other than transcriptional regulation. Our study provides a further understanding of the effects of SV40 transformation on cellular stress responses, and emphasizes the value of SV40-transformed cells in the researches of sensitizing neoplastic cells to radiations.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-09-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0073311PMID 24019915PMCID 3760899
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• THEME: A web tool for loop-design microarray data analysis

  2012cited by this paper
• Proteomic analysis by SILAC and 2D-DIGE reveals radiation-induced endothelial response: four key pathways.

  2012cited by this paper
• SV40 T/t-common polypeptide enhances the sensitivity of HER2-overexpressing human cancer cells to anticancer drugs cisplatin and doxorubicin.

  2012cited by this paper
• Gene Expression Profiling of Dendritic Cells in Different Physiological Stages under Cordyceps sinensis Treatment

  2012cited by this paper
• Identification of a radiosensitivity signature using integrative metaanalysis of published microarray data for NCI-60 cancer cells

  2012cited by this paper
• Downregulation of metallothionein 1F, a putative oncosuppressor, by loss of heterozygosity in colon cancer tissue.

  2012cited by this paper
• Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction

  2012cited by this paper
• miRNA-195 sensitizes human hepatocellular carcinoma cells to 5-FU by targeting BCL-w.

  2011cited by this paper
• Caspase-3-mediated degradation of condensin Cap-H regulates mitotic cell death

  2011cited by this paper
• Condensin association with histone H2A shapes mitotic chromosomes

  2011cited by this paper
• Rapid proteomic remodeling of cardiac tissue caused by total body ionizing radiation

  2011cited by this paper
• Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

  2011cited by this paper
• Sphingosine Kinase-1 Enhances Resistance to Apoptosis through Activation of PI3K/Akt/NF-κB Pathway in Human Non–Small Cell Lung Cancer

  2011cited by this paper
• TSPYL5 suppresses p53 levels and function by physical interaction with USP7

  2011cited by this paper
• Radiation–Induced Signaling Results in Mitochondrial Impairment in Mouse Heart at 4 Weeks after Exposure to X-Rays

  2011cited by this paper
• Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen

  2011cited by this paper
• Repeated Small Perturbation Approach Reveals Transcriptomic Steady States

  2011cited by this paper
• The Menin Tumor Suppressor Protein Is Phosphorylated in Response to DNA Damage

  2011cited by this paper
• Hydrolytic pathway protects against ceramide-induced apoptosis in keratinocytes exposed to UVB.

  2010cited by this paper
• A minority of foci or pan-nuclear apoptotic staining of γH2AX in the S phase after UV damage contain DNA double-strand breaks

  2010cited by this paper
• TSPYL5 is involved in cell growth and the resistance to radiation in A549 cells via the regulation of p21(WAF1/Cip1) and PTEN/AKT pathway.

  2010cited by this paper
• Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function

  2010cited by this paper
• The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein.

  2010cited by this paper
• Transcription-independent p53 apoptosis: an alternative route to death.

  2010cited by this paper
• Amphiregulin promotes BAX inhibition and resistance to gefitinib in non-small-cell lung cancers.

  2010cited by this paper
• MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer.

  2009cited by this paper
• UVB Radiation Induces Persistent Activation of Ribosome and Oxidative Phosphorylation Pathways

  2009influential reference
• A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation.

  2009cited by this paper
• Characterization of DNA damage-dependent cell cycle checkpoints in a menin-deficient model.

  2009cited by this paper
• Blinded by the Light: The Growing Complexity of p53.

  2009cited by this paper
• Cloning and characterization of the 5'UTR of the rat anti-apoptotic Bcl-w gene.

  2009cited by this paper
• p53 and metabolism

  2009cited by this paper
• Cell-type specific regulation of gene expression by simian virus 40 T antigens.

  2009cited by this paper
• Real-time single-molecule observation of rolling-circle DNA replication

  2009cited by this paper
• How the Rb tumor suppressor structure and function was revealed by the study of Adenovirus and SV40.

  2009cited by this paper
• SV40: Cell transformation and tumorigenesis.

  2009cited by this paper
• Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

  2008cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008cited by this paper
• The genetics of the p53 pathway, apoptosis and cancer therapy

  2008cited by this paper
• Simian Virus 40 Large T Antigen Disrupts Genome Integrity and Activates a DNA Damage Response via Bub1 Binding

  2008cited by this paper
• SV40 small T antigen and PP2A phosphatase in cell transformation

  2008cited by this paper
• SV40 T/t-common polypeptide specifically induces apoptosis in human cancer cells that overexpress HER2/neu.

  2006cited by this paper
• Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair.

  2006cited by this paper
• Tumor cell radiosensitivity is a major determinant of tumor response to radiation.

  2006cited by this paper
• TIGAR, a p53-inducible regulator of glycolysis and apoptosis.

  2006cited by this paper
• p53 Regulates Mitochondrial Respiration

  2006cited by this paper
• Cellular UV damage responses--functions of tumor suppressor p53.

  2005cited by this paper
• SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation

  2005cited by this paper
• Transcription-independent pro-apoptotic functions of p53.

  2005cited by this paper
• Involvement of PP2A in viral and cellular transformation

  2005cited by this paper
• Crosslinking of Ribosomal Proteins to RNA in Maize Ribosomes by UV-B and Its Effects on Translation1[w]

  2004cited by this paper
• Regulation of ultraviolet light-induced gene expression by gene size.

  2004cited by this paper
• Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells.

  2003cited by this paper
• UV Induces GADD45 in a p53-Dependent and -Independent Manner in Human Keratinocytes

  2003cited by this paper
• Control of apoptosis by p53

  2003cited by this paper
• GADD45 regulates G2/M arrest, DNA repair, and cell death in keratinocytes following ultraviolet exposure.

  2002cited by this paper
• GADD45-induced cell cycle G2-M arrest associates with altered subcellular distribution of cyclin B1 and is independent of p38 kinase activity

  2002cited by this paper
• p53 regulation of DNA excision repair pathways.

  2002cited by this paper
• Regulation of the G2/M transition by p53

  2001cited by this paper
• The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene

  2000cited by this paper
• The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses.

  1999cited by this paper
• Genomic instability in Gadd45a-deficient mice

  1999cited by this paper
• Effect of DNA lesions on transcription elongation.

  1999cited by this paper
• Persistent DNA damage induced by ultraviolet light inhibits p21waf1 and bax expression: implications for DNA repair, UV sensitivity and the induction of apoptosis

  1998cited by this paper
• DNA-damage-inducible p53 activity in SV40-transformed cells

  1997cited by this paper
• Capacity of UV‐lrradiated Human Fibroblasts to Support Adenovirus DNA Synthesis Correlates with Transcription‐Coupled Repair and is Reduced in SV40‐Transformed Cells and Cells Expressing Mutant p53

  1997cited by this paper
• Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

  1997cited by this paper
• Expression of Wild-type p53 Is Required for Efficient Global Genomic Nucleotide Excision Repair in UV-irradiated Human Fibroblasts*

  1997cited by this paper
• Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion.

  1996cited by this paper
• G2/M-phase arrest and release in ataxia telangiectasia and normal cells after exposure to ionizing radiation.

  1994cited by this paper
• Flow-cytometric detection of changes in the fluorescence emission spectrum of a vital DNA-specific dye in human tumour cells.

  1985cited by this paper
• Radiation: Studies of Mouse Cells Lacking P53-mediated Dna Repair Responses to Uv

  year unknowncited by this paper

• Cancer Cells in all EMT States Lack Rigidity Sensing Depletion of Different Tumor Suppressors Causes Loss of Rigidity Sensing in Cancer Cells

  2022cites this paper
• Global Transcriptional Analysis of Nontransformed Human Intestinal Epithelial Cells (FHs 74 Int) after Exposure to Selected Drinking Water Disinfection By-Products

  2019cites this paper
• Engineered Cationic Antimicrobial Peptides Containing Cholesterol InteractingMotifs to Target Viral Envelopes

  2017cites this paper
• Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

  2014cites this paper
• Distinct Epidermal Keratinocytes Respond to Extremely Low-Frequency Electromagnetic Fields Differently

  2014cites this paper
• Sterigmatocystin induces G1 arrest in primary human esophageal epithelial cells but induces G2 arrest in immortalized cells: key mechanistic differences in these two models

  2014cites this paper
• THEME: A web tool for loop-design microarray data analysis

  2012cites this paper