Liu Hang, Wang Min, Li Min, Wang Donghai, Rao Qing, Wang Yang, Xu Zhifang, Wang Jianxiang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
Biochem Biophys Res Commun. 2008 Oct 24;375(3):477-83. doi: 10.1016/j.bbrc.2008.08.046. Epub 2008 Aug 21.
DJ-1 is a multifunctional protein that has been implicated in pathogenesis of some solid tumors. In this study, we found that DJ-1 was overexpressed in acute leukemia (AL) patient samples and leukemia cell lines, which gave the first clue that DJ-1 overexpression might be involved in leukemogenesis and/or disease progression of AL. Inactivation of DJ-1 by RNA-mediated interference (RNAi) in leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation potential and enhancement of the sensitivity of leukemia cells to chemotherapeutic drug etoposide. Further investigation of DJ-1 activity revealed that phosphatase and tensin homolog (PTEN), as well as some proliferation and apoptosis-related genes, was regulated by DJ-1. Thus, DJ-1 might be involved in leukemogesis through regulating cell growth, proliferation, and apoptosis. It could be a potential therapeutic target for leukemia.
DJ-1是一种多功能蛋白，已被证明与某些实体瘤的发病机制有关。在本研究中，我们发现DJ-1在急性白血病（AL）患者样本和白血病细胞系中过表达，这首次提示DJ-1过表达可能参与AL的白血病发生和/或疾病进展。通过RNA介导的干扰（RNAi）使白血病细胞系K562和HL60中的DJ-1失活，导致白血病细胞增殖潜能受到抑制，并增强了白血病细胞对化疗药物依托泊苷的敏感性。对DJ-1活性的进一步研究表明，磷酸酶和张力蛋白同源物（PTEN）以及一些与增殖和凋亡相关的基因受DJ-1调控。因此，DJ-1可能通过调节细胞生长、增殖和凋亡参与白血病发生。它可能是白血病的一个潜在治疗靶点。
