Transcriptional activation of p21 by vitamin D-3 or vitamin K-2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells

Citation
M. Zenmyo et al., Transcriptional activation of p21 by vitamin D-3 or vitamin K-2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells, HUMAN PATH, 32(4), 2001, pp. 410-416
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
HUMAN PATHOLOGY
ISSN journal
0046-8177 → ACNP
Volume
32
Issue
4
Year of publication
2001
Pages
410 - 416
Database
ISI
SICI code
0046-8177(200104)32:4<410:TAOPBV>2.0.ZU;2-M
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 differentia tion-inducing agents by a p53-independent pathway. These agents induced exp ression of p21 by binding to specific DNA elements and modulating transcrip tional initiation. We demonstrated that the gene encoding p21 was not only a vitamin D-3 target gene but also vitamin K-2 target gene in the cells and that their differentiation was well related to the transcriptional activat ion of the p21 gene. Transient overexpression of p21, using adenovirus-driv en p21 expression plasmid, in MG-63 cells in the absence of vitamins D-3 an d K-2 resulted in their differentiation. The transcriptional activation of p21 by vitamin D-3 or vitamin K-2 in p55-deficient osteosarcoma cells demon strated the p53-independent role of p21 in human osseous differentiation.