Department of Dermatology, Ehime University School of Medicine, Ehime, Japan

Correspondence: Kenshi Yamasaki, Department of Dermatology, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. Email: yamasaki@m.ehime-u.ac.jp

Received 17 September 2003; Revised 10 December 2003; Accepted 6 January 2004.

Abstract

1,25-dihydroxyvitamin D3 (1,25[OH]₂VD3) has an antiproliferative effect on keratinocyte growth, and its derivatives are used for the treatment of psoriasis. It was reported previously that 1,25[OH]₂VD3 induced cell cycle arrest not only at the G0/G1 phase but also at the G2/M phase. However, the mechanism of 1,25[OH]₂VD3-induced G2/M phase arrest in keratinocytes has not been fully understood. The addition of 10^-8 to 10^-6 M 1,25[OH]₂VD3 to cultured normal human keratinocytes enhanced the expression of Myt1 mRNA preceding Wee1 mRNA; 10^-6 M 1,25[OH]₂VD3 unregulated Myt1 mRNA from 6 h to 24 h and Wee1 mRNA from 12 to 48 h. Interestingly, the levels of phosphorylated Cdc2 were increased between 6 h and 48 h after 1,25[OH]₂VD3 treatment, although the expression levels of Cdc2 mRNA and its protein production were reduced. 1,25[OH]₂VD3 also decreased the expression of cyclin B1, which forms a complex with Cdc2. These data indicated that the increase of Myt1 and Wee1 induced the phosphorylation of Cdc2 leading to G2/M arrest. In conclusion, the induction of Cdc2 phosphorylation due to the increase of Wee1 and Myt1 as well as the reduction of Cdc2 and cyclin B1 are involved in 1,25[OH]₂VD3-induced G2/M arrest of keratinocytes.