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Signal Transduction – Tumor Suppressor Genes and Cell Cycle

p21Cip1/WAF1 is important for differentiation and survival of U937 cells

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Abstract

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.

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  1. K Fukumuro

    Present address: Division of Hospital Pharmacy, Tokyo Women’s Medical College, 8-1 Kawado-cho, Shinjuku-ku, Tokyo, Japan

Authors and Affiliations

  1. Department of Virology, The National Children’s Medical Research Center, Tokyo, Japan

    M Asada, T Yamada & S Mizutani

  2. Department of Pharmacotherapeutics, Tokyo Science University, Tokyo, Japan

    K Fukumuro

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  1. M Asada
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  2. T Yamada
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  3. K Fukumuro
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  4. S Mizutani
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Asada, M., Yamada, T., Fukumuro, K. et al. p21Cip1/WAF1 is important for differentiation and survival of U937 cells. Leukemia 12, 1944–1950 (1998). https://doi.org/10.1038/sj.leu.2401228

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  • DOI: https://doi.org/10.1038/sj.leu.2401228

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