Asada M, Yamada T, Fukumuro K, Mizutani S
Department of Virology, The National Children's Medical Research Center, Tokyo, Japan.
Leukemia. 1998 Dec;12(12):1944-50. doi: 10.1038/sj.leu.2401228.
Vitamin D3 (VD3) induces monocytic differentiation of U937 cells. Induction of p21Cip1/WAF1 (p21) and subsequent G0/G1 cell-cycle arrest are required in this process. Using a system of inducible expression of ectopic p21, we demonstrated the important role of p21 in the induction of monocytic differentiation in U937 cells. Prior induction of antisense-p21 expression significantly suppressed p21 expression, and resulted in inhibition of VD3-induced U937 differentiation. Moreover, induction of expression of antisense-p21 in VD3-differentiated U937 cells resulted in apoptosis of the cells. This was associated with activation of Cdc2 and caspase-3 like protease. Our results suggest that p21 is required for the initiation of the early steps of differentiation as well as survival of differentiated cells.
维生素D3（VD3）可诱导U937细胞向单核细胞分化。在此过程中，需要诱导p21Cip1/WAF1（p21）表达并随后使细胞周期停滞于G0/G1期。利用可诱导异位p21表达的系统，我们证明了p21在诱导U937细胞向单核细胞分化过程中的重要作用。预先诱导反义p21表达可显著抑制p21表达，并导致VD3诱导的U937细胞分化受到抑制。此外，在VD3分化的U937细胞中诱导反义p21表达会导致细胞凋亡。这与Cdc2和caspase-3样蛋白酶的激活有关。我们的结果表明，p21对于分化早期步骤的启动以及分化细胞的存活是必需的。
