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Comparative transcriptome profiling of an SV40-transformed human fibroblast (MRC5CVI) and its untransformed counterpart (MRC-5) in response to UVB irradiation.

Chang CW, Chen CR, Huang CY, Shu WY, Chiang CS, Hong JH, Hsu IC - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.

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.

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Summary of similar and dissimilar responses to UVB irradiation of MRC-5 and MRC5CVI.The UVB-induced responses are represented by functions that are (A) similarly or (B) dissimilarly regulated in MRC-5 and MRC5CVI. For example, the regulation of oxidative phosphorylation is similar, whereas the regulation of cell cycle arrest is dissimilar in the two cell types. The transcriptomic results suggest that the apoptosis response is suppressed in MRC5CVI; however, the results of the cell death assays indicate that MRC5CVI is more sensitive to UVB-induced cell death (see the Discussion section).
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pone-0073311-g006: Summary of similar and dissimilar responses to UVB irradiation of MRC-5 and MRC5CVI.The UVB-induced responses are represented by functions that are (A) similarly or (B) dissimilarly regulated in MRC-5 and MRC5CVI. For example, the regulation of oxidative phosphorylation is similar, whereas the regulation of cell cycle arrest is dissimilar in the two cell types. The transcriptomic results suggest that the apoptosis response is suppressed in MRC5CVI; however, the results of the cell death assays indicate that MRC5CVI is more sensitive to UVB-induced cell death (see the Discussion section).

Mentions: We investigated the UVB-responsive transcriptome of MRC5CVI and MRC-5. Based on the results of functional enrichment analysis, the literature review, cell cycle analysis, and cell death analysis, we summarized their responses to UVB irradiation into similar and dissimilar regulated functions (Figure 6A and 6B, respectively). In response to UVB irradiation, MRC5CVI was still able to up-regulate the expression of oxidative phosphorylation genes as MRC-5 was (Figure 6A and Figure S2). Furthermore, MRC5CVI failed to regulate the expression of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes in human fibroblasts (Figure 6B). Our results of the cell death assays revealed that MRC5CVI was more sensitive to UVB-induced cell death than MRC-5, which is in agreement with the results of previous studies, which showed that SV40-transformed cells are more sensitive to radiation than their untransformed counterparts (see the following discussion) [23]–[24].


Comparative transcriptome profiling of an SV40-transformed human fibroblast (MRC5CVI) and its untransformed counterpart (MRC-5) in response to UVB irradiation.

Chang CW, Chen CR, Huang CY, Shu WY, Chiang CS, Hong JH, Hsu IC - PLoS ONE (2013)

Summary of similar and dissimilar responses to UVB irradiation of MRC-5 and MRC5CVI.The UVB-induced responses are represented by functions that are (A) similarly or (B) dissimilarly regulated in MRC-5 and MRC5CVI. For example, the regulation of oxidative phosphorylation is similar, whereas the regulation of cell cycle arrest is dissimilar in the two cell types. The transcriptomic results suggest that the apoptosis response is suppressed in MRC5CVI; however, the results of the cell death assays indicate that MRC5CVI is more sensitive to UVB-induced cell death (see the Discussion section).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760899&req=5

pone-0073311-g006: Summary of similar and dissimilar responses to UVB irradiation of MRC-5 and MRC5CVI.The UVB-induced responses are represented by functions that are (A) similarly or (B) dissimilarly regulated in MRC-5 and MRC5CVI. For example, the regulation of oxidative phosphorylation is similar, whereas the regulation of cell cycle arrest is dissimilar in the two cell types. The transcriptomic results suggest that the apoptosis response is suppressed in MRC5CVI; however, the results of the cell death assays indicate that MRC5CVI is more sensitive to UVB-induced cell death (see the Discussion section).
Mentions: We investigated the UVB-responsive transcriptome of MRC5CVI and MRC-5. Based on the results of functional enrichment analysis, the literature review, cell cycle analysis, and cell death analysis, we summarized their responses to UVB irradiation into similar and dissimilar regulated functions (Figure 6A and 6B, respectively). In response to UVB irradiation, MRC5CVI was still able to up-regulate the expression of oxidative phosphorylation genes as MRC-5 was (Figure 6A and Figure S2). Furthermore, MRC5CVI failed to regulate the expression of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes in human fibroblasts (Figure 6B). Our results of the cell death assays revealed that MRC5CVI was more sensitive to UVB-induced cell death than MRC-5, which is in agreement with the results of previous studies, which showed that SV40-transformed cells are more sensitive to radiation than their untransformed counterparts (see the following discussion) [23]–[24].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.

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.

Show MeSH
Related in: MedlinePlus