Wang Jiying, Rao Qing, Wang Min, Wei Hui, Xing Haiyan, Liu Hang, Wang Yanzhong, Tang Kejing, Peng Leiwen, Tian Zheng, Wang Jianxiang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Biochem Biophys Res Commun. 2009 Sep 4;386(4):769-74. doi: 10.1016/j.bbrc.2009.06.125. Epub 2009 Jun 27.
Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.
Rac1属于Rho家族,是控制细胞迁移和增殖的信号通路的关键介质,有助于造血干细胞与其微环境的相互作用。Rac1的改变可能导致相互作用失衡,最终导致白血病发生。在本研究中,我们分析了白血病患者中Rac1蛋白的表达,并确定其在白血病细胞异常行为中的作用。与正常骨髓单个核细胞相比,Rac1蛋白在原发性急性髓系白血病细胞中过表达。在白血病细胞系中,siRNA介导沉默Rac1可诱导细胞迁移、增殖和集落形成受到抑制。此外,用Rac1-GTPase抑制剂NSC23766阻断Rac1活性可抑制细胞迁移和生长。我们得出结论,Rac1的过表达有助于白血病细胞加速迁移和具有高增殖潜能,这可能与白血病的发生和进展有关。