Keratinocyte G2/M growth arrest by 1,25-dihydroxyvitamin D3 is caused by Cdc2 phosphorylation through Wee1 and Myt1 regulation

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:122

Article

Dai, X ; Yamasaki, K ; Yang, LJ ; Sayama, K ; Shirakata, Y ; Tokumara, S ; Yahata, Y ; Tohyama, M ; Hashimoto, K

关键词: 1,25-dihydroxyvitamin D3;    Keratinocyte;    Wee1;    Myt1;    Cdc2;    cell cycle;   

DOI  :  10.1111/j.0022-202X.2004.22522.x

来源: Elsevier

【 摘 要 】

1,25-dihydroxyvitamin D3 (1,25[OH](2)VD3) 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](2)VD3 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](2)VD3-induced G2/M phase arrest in keratinocytes has not been fully understood. The addition of 10(-8) to 10(-6) M 1,25[OH](2)VD3 to cultured normal human keratinocytes enhanced the expression of Myt1 mRNA preceding Wee1 mRNA; 10(-6) M 1,25[OH](2)VD3 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](2)VD3 treatment, although the expression levels of Cdc2 mRNA and its protein production were reduced. 1,25[OH](2)VD3 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](2)VD3-induced G2/M arrest of keratinocytes.

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