title: Comparative transcriptome profiling of an SV40-transformed human fibroblast (MRC5CVI) and its untransformed counterpart (MRC-5) in response to UVB irradiation.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Chaang-Ray
authors.initials: CR
authors.lastname: Chen
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Huang
authors.forename: Wun-Yi
authors.initials: WY
authors.lastname: Shu
authors.forename: Chi-Shiun
authors.initials: CS
authors.lastname: Chiang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Hong
authors.forename: Ian C
authors.initials: IC
authors.lastname: Hsu
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002461:Cell Line, Transformed; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects; D020869:Gene Expression Profiling; D006801:Humans; D059467:Transcriptome; D014466:Ultraviolet Rays
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