Loss of p21(Sdi1) expression in senescent cells after DNA damage accompanied with increase of miR-93 expression and reduced p53 interaction with p21(Sdi1) gene promoter |
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Authors: | Choi Ok Ran Lim In Kyoung |
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Institution: | Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea. |
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Abstract: | To answer what is a critical event for higher incidence of tumor development in old than young individuals, primary culture of human diploid fibroblasts were employed and DNA damage was induced by doxorubicin or X-ray irradiation. Response to the damage was different between young and old cells; loss of p21(sdi1) expression in spite of p53(S1?) activation in old cells along with 3H]thymidine and BrdU incorporation, but not in young cells. The phenomenon was confirmed by other tissue fibroblasts obtained from different donor ages. Induction of miR-93 expression and reduced p53 binding to p21 gene promoter account for loss of p21(sdi1) expression in senescent cells after DNA damage, suggesting a mechanism of in vivo carcinogenesis in aged tissue without repair arrest. |
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