Effect of G-rich oligonucleotides on the proliferation of leukemia cells and its relationship with p53 expression.
G-rich oligonucleotides (GROs) can inhibit cell proliferation by inducing cell cycle arrest at S phase in tumor cell lines. GROs bind specific cellular proteins, such as nucleolin, a crucial protein interacting with P53; however, little is known about the relationship between GROs and P53. In this study, we have shown that GROs inhibited the proliferation of U937 cells (a human monocytic leukemia cell line without P53 expression) by inducing S-phase arrest. We also showed that GRO colocalized with nucleolin in U937 cells. GRO treatment induced alteration of a series of cell cycle regulatory proteins in U937 cells. Increased Cdk2 expression might promote the cells to enter S phase and subsequent decrease of Cdk2 might induce cell cycle arrest in S phase. Transfection of U937 cells with a wild-type p53 gene caused the formation of nucleolin-P53 complex, which alleviated the effect of GRO on leukemia cells. This alleviated effect is probably due to the decreased uptake of GRO.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
Lei
L
Zhi
Jianwei
J
Zhang
Yujiao
Y
Jia
Shilong
S
Shan
Yan
Y
Li
Donghai
D
Wang
Min
M
Wang
Qing
Q
Rao
Haiyan
H
Xing
Kejing
K
Tang
Zheng
Z
Tian
Jianxiang
J
Wang
Yingchang
Y
Mi
D001692:Biological Transport / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D000097796:Nucleolin
D051357:Cyclin-Dependent Kinase 2; D016213:Cyclins; D009841:Oligonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D000097796:Nucleolin; C495894:CDK2 protein, human