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: M Zenmyo, S Komiya, T Hamada, K Hiraoka, S Kato, T Fujii, H Yano, K Irie, K Nagata
• Journal: Human pathology (Hum Pathol) Vol. 32 Issue 4 Pg. 410-6 (Apr 2001) ISSN: 0046-8177 [Print] United States
• PMID: 11331958 (Publication Type: Journal Article)
• Copyright: Copyright 2001 by W.B. Saunders Company

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins

Topics

• Bone Neoplasms (genetics, pathology)
• Cell Differentiation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, p53
• Humans
• Osteosarcoma (genetics, pathology)
• Transcriptional Activation (drug effects)
• Tumor Cells, Cultured