Brooks S C, Sturgill R, Choi J, Yen A
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Exp Cell Res. 1997 Aug 1;234(2):259-69. doi: 10.1006/excr.1997.3620.
NB4, a human acute promyelocytic leukemia cell line expressing the promyelocyte-retinoic acid receptor alpha (PML-RAR alpha) hybrid protein was treated with RAR- and retinoid X receptor (RXR)-selective analogs to determine their effects on cell proliferation, retinoblastoma (RB) tumor-suppressor protein phosphorylation, and differentiation. An RAR- or just RAR alpha-selective analog alone induced similar cell population growth arrest, cell cycle arrest without restriction to G1, hypophosphorylation of RB, and myelomonocytic cell surface differentiation marker expression (CD11b). In addition, an RAR alpha antagonist could inhibit the effects of the RAR alpha agonist completely. The RAR alpha-selective analog-elicited response was attenuated by simultaneous addition of various RXR-selective analogs. In contrast, each of the RXR-selective analogs was unable to induce any of the cellular responses analyzed. The growth arrest of NB4 cells is not G1-restricted and occurs at all points in the cell cycle. Cells growth arrested by treatment with an RAR alpha-selective analog show primarily hypophosphorylated RB. When these cells are sorted into G1 or S + G2/M subpopulations by flow cytometry, hypophosphorylated RB protein was in G1 as well as S + G2/M cells. This suggests that the hypophosphorylated RB protein may be mediating the growth arrest of NB4 cells at all points in the cell cycle. These results are consistent with an involvement of PML-RAR alpha and/or RAR alpha in the transduction of the retinoid signal in NB4 cells.
NB4是一种表达早幼粒细胞-维甲酸受体α（PML-RARα）融合蛋白的人类急性早幼粒细胞白血病细胞系，用维甲酸受体（RAR）和视黄酸X受体（RXR）选择性类似物处理该细胞系，以确定它们对细胞增殖、视网膜母细胞瘤（RB）肿瘤抑制蛋白磷酸化及分化的影响。单独使用一种RAR或仅RARα选择性类似物可诱导相似的细胞群体生长停滞、无G1期限制的细胞周期停滞、RB的低磷酸化以及骨髓单核细胞表面分化标志物表达（CD11b）。此外，一种RARα拮抗剂可完全抑制RARα激动剂的作用。同时添加各种RXR选择性类似物可减弱RARα选择性类似物引发的反应。相反，每种RXR选择性类似物均无法诱导所分析的任何细胞反应。NB4细胞的生长停滞并非受G1期限制，而是发生在细胞周期的所有阶段。用RARα选择性类似物处理导致生长停滞的细胞主要显示RB低磷酸化。当通过流式细胞术将这些细胞分选到G1期或S+G2/M亚群时，G1期以及S+G2/M期细胞中均存在低磷酸化的RB蛋白。这表明低磷酸化的RB蛋白可能在细胞周期的所有阶段介导NB4细胞的生长停滞。这些结果与PML-RARα和/或RARα参与NB4细胞中类视黄醇信号转导一致。
