title: Transcriptional activation of p21 by vitamin D(3) or vitamin K(2) leads to differentiation of p53-deficient MG-63 osteosarcoma cells.
abstract: p21 (WAF1/CIP1) is a downstream effector of p53 and mediates growth arrest by inhibiting the action of G(1) cyclin-dependent kinases. However, it has been reported that the p21 expression was triggered by multiple differentiation-inducing agents by a p53-independent pathway. These agents induced expression of p21 by binding to specific DNA elements and modulating transcriptional initiation. We demonstrated that the gene encoding p21 was not only a vitamin D(3) target gene but also a vitamin K(2) target gene in the cells and that their differentiation was well related to the transcriptional activation of the p21 gene. Transient overexpression of p21, using adenovirus-driven p21 expression plasmid, in MG-63 cells in the absence of vitamins D(3) and K(2) resulted in their differentiation. The transcriptional activation of p21 by vitamin D(3) or vitamin K(2) in p53-deficient osteosarcoma cells demonstrated the p53-independent role of p21 in human osseous differentiation. HUM PATHOL 32:410-416.
authors.affiliation: Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Zenmyo
authors.forename: S
authors.initials: S
authors.lastname: Komiya
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: K
authors.initials: K
authors.lastname: Hiraoka
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Irie
authors.forename: K
authors.initials: K
authors.lastname: Nagata
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins