title: 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.
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(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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Ok Ran
authors.initials: OR
authors.lastname: Choi
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53