NDRG2 in rat liver regeneration: Role in proliferation and apoptosis

被引:27
作者
Yang, Jiandong [1 ]
Li, Yan [2 ]
Wu, Lin [2 ]
Zhang, Zhaoxia [4 ]
Han, Tenglong [2 ]
Guo, Hang [3 ]
Jiang, Ning [3 ]
Tao, Kaishan [1 ]
Ti, Zhenyu [1 ]
Liu, Xinping [2 ]
Yao, Libo [2 ]
Dou, Kefeng [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, State Key Lab Canc Biol, Dept Biochem & Mol Biol, Xian 710032, Peoples R China
[3] Fourth Mil Med Univ, Xijing Hosp, Dept Oncol, Xian 710032, Peoples R China
[4] Shanxi Med Univ, Clin Med Hosp 1, Dept Ophthalmol, Taiyuan, Peoples R China
基金
中国国家自然科学基金;
关键词
CYCLIN-DEPENDENT KINASES; DOWNSTREAM-REGULATED GENE-2; CORE PROMOTER; MOUSE EMBRYO; CELL-CYCLE; MYC; EXPRESSION; CANCER; REPRESSION; INHIBITORS;
D O I
10.1111/j.1524-475X.2010.00614.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Liver regeneration is a complex process that is orchestrated by the precise interplay of cell proliferation, differentiation control, and molecular pathways, but this complicated molecular signaling network is not fully understood. In this study, we showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in this process. The mRNA and protein levels of NDRG2 were strongly reduced when liver regeneration reached a peak of activity. In addition, we found that rat NDRG2 expression and C-Myc expression were inversely correlated during this process. A low level of NDRG2 was observed as the C-Myc expression increased during regeneration. Moreover, a dramatic cell cycle arrest was found in normal rat liver-derived BRL cells 48 hours after being infected by adenoviral vectors expressing rat NDRG2. Meanwhile, the apoptotic rates were increased from 9.4% in control group to 64.7% in adenoviral vectors expressing rat NDRG2 group. These phenomena could also be observed in BRL 3A and L-02 cells. Further analysis revealed that NDRG2 overexpression may mediate the antiproliferative effect by inducing p53 and p21 regulated Bax/Bcl-2 increase and cyclin E-Cdk2 inhibition. In conclusion, our findings point to physiological roles for NDRG2 in liver regeneration.
引用
收藏
页码:524 / 531
页数:8
相关论文
共 36 条
  • [1] Arora V, 2000, J PHARMACOL EXP THER, V292, P921
  • [2] MAX - A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT FORMS A SEQUENCE-SPECIFIC DNA-BINDING COMPLEX WITH MYC
    BLACKWOOD, EM
    EISENMAN, RN
    [J]. SCIENCE, 1991, 251 (4998) : 1211 - 1217
  • [3] Characterization of rat NDRG2 (N-Myc downstream regulated gene 2), a novel early mineralocorticoid-specific induced gene
    Boulkroun, S
    Fay, M
    Zennaro, MC
    Escoubet, B
    Jaisser, F
    Blot-Chabaud, M
    Farman, N
    Courtois-Coutry, N
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (35) : 31506 - 31515
  • [4] Liver regeneration
    Diehl, AM
    [J]. FRONTIERS IN BIOSCIENCE-LANDMARK, 2002, 7 : E301 - E314
  • [5] Proliferation, cell cycle and apoptosis in cancer
    Evan, GI
    Vousden, KH
    [J]. NATURE, 2001, 411 (6835) : 342 - 348
  • [6] KINETICS OF CELLULAR PROLIFERATION IN REGENERATING LIVER
    FABRIKANT, JI
    [J]. JOURNAL OF CELL BIOLOGY, 1968, 36 (03) : 551 - +
  • [7] Liver regeneration
    Fausto, N
    Campbell, JS
    Riehle, KJ
    [J]. HEPATOLOGY, 2006, 43 (02) : S45 - S53
  • [8] Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells
    Fausto, N
    [J]. HEPATOLOGY, 2004, 39 (06) : 1477 - 1487
  • [9] Fausto Nelson, 1994, P1059
  • [10] HARPER JW, 1993, CELL, V75, P805