Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth.
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.
Wang
Jiying
J
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.
Rao
Qing
Q
Wang
Min
M
Wei
Hui
H
Xing
Haiyan
H
Liu
Hang
H
Wang
Yanzhong
Y
Tang
Kejing
K
Peng
Leiwen
L
Tian
Zheng
Z
Wang
Jianxiang
J
D000634:Aminoquinolines / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D014410:Tumor Stem Cell Assay; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D000634:Aminoquinolines; C487513:NSC 23766; D011743:Pyrimidines; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein