Inhibiting CCN1 blocks AML cell growth by disrupting the MEK/ERK pathway

Cancer Cell International

Wei-Ke Si¹  Chen Zhao¹  Jing Pan¹  Xiao-Li Zhang¹  Zhong Yang¹  Chen Zhao²  Chang-Chun Niu³ 

[1] Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China;The First Affiliated Hospital, Chongqing Medical University, Chongqing 400042, China;Department of Clinical Laboratory, The Third People’s Hospital of Chongqing, Chongqing 400014, China

关键词: ERK;    AML;    CCN1;   

Others  :  1121672
DOI  :  10.1186/s12935-014-0074-z

 received in 2014-02-26, accepted in 2014-07-21,  发布年份 2014

【 摘 要 】

Background

CCN1 plays distinct roles in various tumor types, but little is known regarding the role of CCN1 in leukemia.

Methods

We analyzed CCN1 protein expression in leukemia cell lines and in AML bone marrow samples. We also evaluated the effects of antibody- or siRNA-mediated inhibition of CCN1 on the growth of two AML cell lines (U937 and Kasumi-1 cells) and on the MEK/ERK pathway, β-catenin and other related genes.

Results

U937 and Kasumi-1 cells had markedly higher CCN1 expression than the 5 other leukemia cell lines, and CCN1 protein expression was higher in the AML bone marrow samples than in the normal bone marrow samples. Blocking CCN1 with an antibody in U937 and Kasumi-1 cells suppressed proliferation, increased apoptosis, down-regulated Bcl-xL and c-Myc expression, up-regulated Bax expression, and had no effect on Survivin. siRNA-mediated down-regulation of CCN1 inhibited the proliferation and colony formation of U937 and Kasumi-1 cells and increased cytarabine-induced apoptosis. Furthermore, CCN1 siRNA reduced MEK and ERK phosphorylation without affecting β-catenin; the CCN1 antibody similarly affected MEK and ERK phosphorylation. These changes in phosphorylation could influence the expression of Bcl-xL, c-Myc and Bax in AML cells.

Conclusions

The data suggested that CCN1 is a tumor promoter in AML that acts through the MEK/ERK pathway to up-regulate c-Myc and Bcl-xL and to down-regulate Bax.

【 授权许可】

   
2014 Niu et al.; licensee Springer

【 图 表 】

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