Yen A, Powers V, Fishbaugh J
Leuk Res. 1986;10(6):619-29. doi: 10.1016/0145-2126(86)90264-x.
The capability of HL-60 cells to undergo G1/0 specific growth arrest and myeloid differentiation in response to isomers of retinoic acid (RA) having an altered alkyl chain was determined. At a concentration where beta-all trans RA induces myeloid differentiation and G1/0 specific growth arrest, 11,13-dicis and 9,13-dicis isomers failed to induce significant phenotypic differentiation, assayed by the inducible superoxide production characteristic of mature myeloid cells, but could induce moderate G1/0 specific growth arrest. The 9-cis and 11-cis isomers induced both phenotypic differentiation and G1/0 specific growth arrest. The occurrence of G1/0 specific growth arrest without phenotypic differentiation indicates that the induced cellular programs leading to phenotypic differentiation and G1/0 specific growth arrest are not tightly coupled. Within the 48-h period usually required by beta-all trans RA to induce onset of phenotypic differentiation and G1/0 specific growth arrest, all isomers could complete early events in the cellular programs leading to G1/0 specific growth arrest and phenotypic differentiation, but the dicis isomers could not complete late events in the phenotypic differentiation program. The capability of dicis isomers to drive late events in the G1/0 specific growth arrest program was also compromised. Characteristic early and late changes in Ca2+ binding cytosolic proteins induced by RA and its isomers were consistent with their early and late capabilities. Failure of the dicis isomers to induce differentiation was thus due to a failure in late events associated with aberrations in cytosolic, Ca2+ binding proteins. The results suggest a model in which RA presents two signals to induce HL-60 terminal differentiation.
测定了HL-60细胞对具有改变烷基链的视黄酸（RA）异构体作出G1/0特异性生长停滞和髓系分化反应的能力。在β-全反式RA诱导髓系分化和G1/0特异性生长停滞的浓度下，11,13-二顺式和9,13-二顺式异构体未能诱导显著的表型分化（通过成熟髓系细胞的可诱导超氧化物产生特性进行测定），但可诱导中度的G1/0特异性生长停滞。9-顺式和11-顺式异构体既诱导表型分化，也诱导G1/0特异性生长停滞。G1/0特异性生长停滞而无表型分化的发生表明，导致表型分化和G1/0特异性生长停滞的诱导细胞程序并非紧密耦合。在β-全反式RA通常诱导表型分化和G1/0特异性生长停滞开始所需的48小时内，所有异构体均可完成导致G1/0特异性生长停滞和表型分化的细胞程序中的早期事件，但二顺式异构体无法完成表型分化程序中的晚期事件。二顺式异构体驱动G1/0特异性生长停滞程序晚期事件的能力也受到损害。RA及其异构体诱导的Ca2+结合胞质蛋白的特征性早期和晚期变化与其早期和晚期能力一致。因此，二顺式异构体未能诱导分化是由于与胞质Ca2+结合蛋白异常相关的晚期事件失败。结果提示了一个模型，其中RA呈现两个信号来诱导HL-60终末分化。
