TY - JOUR
T1 - The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses
AU - Kohli, Manu
AU - Jorgensen, Timothy J.
N1 - Funding Information:
We gratefully acknowledge H. Tian and P. Russell for helpful discussions. This work was supported by Grant 9307-0016 from the National Aeronautics and Space Administration and P01-CA74175 from the National Cancer Institute of the National Institutes of Health, U.S. DHHS. Flow cytometry work was supported in part by the Lombardi Cancer Center Flow Cytometry/Cell Sorting Shared Resource, U.S. Public Health Service Grant 2P30-CA-51008.
PY - 1999/4/2
Y1 - 1999/4/2
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell cycle
KW - SV40
KW - p21
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=0033515757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033515757&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0389
DO - 10.1006/bbrc.1999.0389
M3 - Article
C2 - 10092528
AN - SCOPUS:0033515757
SN - 0006-291X
VL - 257
SP - 168
EP - 176
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -