Dou Q P, Lui V W
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15213-2582, USA.
Cancer Res. 1995 Nov 15;55(22):5222-5.
Hypophosphorylation of retinoblastoma protein (RB) accompanies the DNA damage-induced, p53-independent G1 arrest and apoptosis in two p53-null human leukemic cell lines, HL-60 and U937 (Q.P. Dou et al., Proc. Natl. Acad. Sci. USA, 92: 9019-9023, 1995). When an HL-60 cell line resistant to cytosine arabinoside was exposed to this DNA-damaging agent, neither RB hypophosphorylation nor apoptosis were observed. In contrast, treatment of these cells with another DNA-damaging agent, etoposide, dramatically induced these events, which were inhibitable by the addition of zinc chloride, a protein tyrosine phosphatase inhibitor. Induction of hypophosphorylation of RB may be an important novel strategy for treating drug-resistant cancers.
视网膜母细胞瘤蛋白（RB）的低磷酸化伴随着DNA损伤诱导的、不依赖p53的G1期阻滞以及两种p53缺失的人白血病细胞系HL-60和U937的凋亡（Q.P. Dou等人，《美国国家科学院院刊》，92: 9019 - 9023, 1995）。当对阿糖胞苷耐药的HL-60细胞系暴露于这种DNA损伤剂时，未观察到RB低磷酸化和凋亡。相反，用另一种DNA损伤剂依托泊苷处理这些细胞，显著诱导了这些事件，而添加蛋白酪氨酸磷酸酶抑制剂氯化锌可抑制这些事件。诱导RB低磷酸化可能是治疗耐药癌症的一种重要新策略。
