Bürger C, Wick M, Müller R
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Germany.
J Cell Sci. 1994 Jul;107 ( Pt 7):2047-54. doi: 10.1242/jcs.107.7.2047.
We have analysed the expression of 7 cyclin and cyclin-associated kinase (cdk) genes in the human myeloid cell line HL-60 at different stages of the cell cycle in non-synchronised cells and during terminal differentiation. A clear cell cycle-dependent expression was found with cyclins A (S+G2), B (G2) and E (late G1 and S), while other cell cycle genes showed only very weak (cdk2) or no periodic expression (cyclin D1, cyclin D2 and cdk4). Induction of macrophage-like differentiation by TPA or granulocytic differentiation by retinoic acid or DMSO was accompanied by a block in G1 and resulted in distinct patterns of gene expression that were lineage- and inducer-specific. These included: (i) a dramatic decrease in the expression of cyclin A, cyclin B and cdk2, and surprisingly an up-regulation of cyclin D1 in TPA-induced macrophage-like cells; (ii) a down-regulation of cyclin E in retinoic acid-induced granulocytic cells; and (iii) a decreased abundance of cyclin D1 and D2, but high levels of cyclin A, B and E RNA in DMSO-induced granulocytic cells. These observations suggest that the mechanisms leading to a differentiation-associated cell cycle arrest are lineage-specific, and that the sustained expression of cyclin and cdk genes does not interfere with the induction of terminal differentiation.
我们分析了7种细胞周期蛋白及细胞周期蛋白相关激酶（cdk）基因在人髓系细胞系HL-60中的表达情况，这些基因在非同步化细胞的细胞周期不同阶段以及终末分化过程中表达。我们发现细胞周期蛋白A（S期+G2期）、B（G2期）和E（G1期末期和S期）呈现明显的细胞周期依赖性表达，而其他细胞周期基因仅表现出非常微弱的（cdk2）或无周期性表达（细胞周期蛋白D1、细胞周期蛋白D2和cdk4）。佛波酯（TPA）诱导巨噬细胞样分化、视黄酸或二甲基亚砜（DMSO）诱导粒细胞分化均伴随着G1期阻滞，并导致特定谱系和诱导剂特异性的基因表达模式。这些模式包括：（i）在TPA诱导的巨噬细胞样细胞中，细胞周期蛋白A、细胞周期蛋白B和cdk2的表达显著降低，而令人惊讶的是细胞周期蛋白D1上调；（ii）在视黄酸诱导的粒细胞中，细胞周期蛋白E下调；（iii）在DMSO诱导的粒细胞中，细胞周期蛋白D1和D2丰度降低，但细胞周期蛋白A、B和E的RNA水平较高。这些观察结果表明，导致分化相关细胞周期阻滞的机制具有谱系特异性，并且细胞周期蛋白和cdk基因的持续表达并不干扰终末分化的诱导。
