期刊
CELL STRUCTURE AND FUNCTION
卷 25, 期 2, 页码 103-113出版社
JAPAN SOC CELL BIOLOGY
DOI: 10.1247/csf.25.103
关键词
apoptosis; differentiation; retinoic acid; HL-60 cell; RPS3a; nbl; actinomycin D
类别
The efficacy of anticancer agents significantly depends on the differential susceptibility of undifferentiated cancer cells and differentiated normal cells to undergo apoptosis, We previously found that enhanced expression of RPS3a/nbl, which apparently encodes a ribosomal protein, seems to prime cells for apoptosis, while suppressing such enhanced expression triggers cell death, The present study found that HL-60 cells induced to differentiate by all-trans retinoic acid did not undergo apoptosis following treatment with actinomycin D whereas undifferentiated HL-60 cells were highly apoptosis-susceptible, confirming earlier suggestions that differentiated cells have diminished apoptosis-susceptibility. Undifferentiated HL-60 cells highly expressed RPS3a/nbl whereas all-trans retinoic acid-induced differentiated cells exhibited markedly reduced levels, suggesting that apoptosis-resistance of differentiated cells could be due to low RPS3a/nbl expression. Down-regulation of enhanced RPS3a/nbl expression was also observed in cc Ils induced to differentiate with the retinoid 4-[(E)-2-(5,6,7,8-tetrahyd ro-5,5,8,8-tetramethyl-2-napthalenyl)-1 -propenyl]benzoic acid without any significant induction of cell death, While downregulation of RPS3a/nbl expression during differentiation did not apparently induce apoptosis, RPS3a/nbl antisense ollgomers triggered death of undifferentiated HL-60 cells, but not of retinoid-induced differentiated cells. It therefore seems that while down-regulation of enhanced RPS3a/nbl expression can induce apoptosis in undifferentiated cells, down-regulation of enhanced RPS3a/nbl expression during differentiation occurs independently of apoptosis, and could be regarded as reverting the primed condition to the unprimed (low RPS3a/nbl) state.
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