An RXR-selective analog attenuates the RAR alpha-selective analog-induced differentiation and non-G(1)-restricted growth arrest of NB4 cells
An RXR-selective analog attenuates the RAR alpha-selective analog-induced differentiation and non-G(1)-restricted growth arrest of NB4 cells
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DOI：
10.1006/excr.1997.3620
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发表时间：
1997-08-01
影响因子：
3.7
通讯作者：
Yen, A
中科院分区：
文献类型：
--
作者：
Brooks, SC;Sturgill, R;Yen, A
NB 4是一种表达早幼粒细胞-视黄酸受体α（PML-RAR α）杂合蛋白的人急性早幼粒细胞白血病细胞系，用RAR和类维生素A X受体（RXR）选择性类似物处理NB 4，以确定其对细胞增殖、视网膜母细胞瘤（RE）肿瘤抑制蛋白磷酸化和分化的影响。RAR-或仅RAR α-选择性类似物单独诱导类似的细胞群体生长停滞、细胞周期停滞（不限于G（1））、RB磷酸化不足和骨髓单核细胞表面分化标志物表达（CD 11b）。此外，RAR α拮抗剂可以完全抑制RAR α激动剂的作用。RAR α选择性类似物引发的反应通过同时加入各种RXR选择性类似物来减弱。相比之下，每种RXR选择性类似物不能诱导所分析的任何细胞应答。NB 4细胞的生长停滞不是G（1）限制性的，并且发生在细胞周期的所有点。通过用RAR α选择性类似物处理而停滞的细胞生长主要显示低磷酸化RE。流式细胞仪将这些细胞分为G（1）或S + G（2）/M两个亚群时，G（1）和S + G（2）/M细胞中均存在低磷酸化的RE蛋白。这表明低磷酸化RE蛋白可能在细胞周期的所有点介导NB 4细胞的生长停滞。这些结果与PML-RAR α和/或RAR α参与NB 4细胞中类维生素A信号的转导一致。(C)北京：科学出版社.
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 (RE) 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 G(1), 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 G(1)-restricted and occurs at all points in the cell cycle, Cells growth arrested by treatment with an RAR alpha-selective analog show primarily hypophosphorylated RE. When these cells are sorted into G(1) or S + G(2)/M subpopulations by flow cytometry, hypophosphorylated RE protein was in G(1) as well as S + G(2)/M cells. This suggests that the hypophosphorylated RE 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. (C) 1997 Academic Press.