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

• Published in: Biochemical and biophysical research communications 2011-04, Vol.407 (2), p.406-411
• Main Authors: Choi, Ok Ran, Lim, In Kyoung
• Format: Article
• Language: English
• Subjects: Adult; Aged; ANIMAL TISSUES; BIOLOGICAL REPAIR; CARCINOGENESIS; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Cells, Cultured; Cellular Senescence - genetics; Child, Preschool; Cyclin-Dependent Kinase Inhibitor p21 - genetics; DNA; DNA Damage; DNA DAMAGES; DOXORUBICIN; FIBROBLASTS; Fibroblasts - drug effects; Fibroblasts - pathology; Fibroblasts - radiation effects; Gene Expression Regulation, Neoplastic; GENES; Humans; IN VIVO; IRRADIATION; Male; MicroRNAs - genetics; Middle Aged; MONOCLINIC LATTICES; NEOPLASMS; Promoter Regions, Genetic; PROMOTERS; RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; THYMIDINE; TRITIUM; Tumor Suppressor Protein p53 - metabolism; Young Adult
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.03.038

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(S¹⁵) 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.