Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Implication of CDK Inhibitors p21 and p27 in the Differentiation of HL-60 Cells
Nobuyuki HorieTsuyoshi MoriHidetsugu AsadaAki IshikawaPatrick G.JohnstonKeiichi Takeishi
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2004 Volume 27 Issue 7 Pages 992-997

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Abstract

All-trans retinoic acid (ATRA) differentiates HL-60 cells into granulocyte-like cells and cellular proliferation is repressed markedly along with the morphological and physiological changes specific for cellular differentiation. To elucidate the implication of cyclin-dependent kinase (CDK) inhibitors during differentiation, we examined the expression of CDK inhibitors during the differentiation of HL-60 cells. The expression of p21 and p27 among the CDK inhibitors we examined increased during the differentiation induced with ATRA. Then, we established stable transformants of HL-60 cells expressing antisense RNA for p21 and p27 and examined the ability of these cells to differentiate into granulocyte-like cells. The extents of fully differentiated HL-60 cells transfected with genes for antisense RNA of p21 and p27 were only 53% and 60%, respectively, whereas 90% of the parental HL-60 cells differentiated by the ATRA treatment. These results suggest that increased expression of CDK inhibitors, p21 and p27, is necessary for the differentiation of HL-60 cells induced with ATRA.

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© 2004 The Pharmaceutical Society of Japan
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