The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses.
The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses.
Kohli
M
M
Division of Radiation Research, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, N.W., Washington, DC 20007-2197, USA.
Jorgensen
T J
TJ
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects; D001260:Ataxia Telangiectasia / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004249:DNA Damage / Q000528:radiation effects; D053938:DNA Fragmentation / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005434:Flow Cytometry; D016193:G1 Phase / Q000528:radiation effects; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D011839:Radiation, Ionizing; D013539:Simian virus 40 / Q000502:physiology*; D015533:Transcriptional Activation / Q000528:radiation effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)