NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498.
BACKGROUND
Recently, the anti-tumor activity of N-myc downstream-regulated gene 2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma (CCRCC), but the role of the down-expression of NDRG2 has not been described.


METHODS
The NDRG2 recombinant adenovirus plasmid was constructed. The proliferation rate and NDRG2 expression of cell infected with recombinant plasmid were mesured by MTT, Flow cytometry analysis and western blot.


RESULTS
The CCRCC cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and significantly decreased the proliferation rate. Fluorescence activated cell sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were in G1-phase compared to 54.39% of control cells (P < 0.05). In addition, there were much more apoptotic cells in NDRG2-expressing cells than in the controls (P < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected examined by western blot. Furthermore, we found that p53 could upregulate NDRG2 expression in A-498 cell.


CONCLUSIONS
We found that NDRG2 can inhibit the proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can up-regulate the expression of NDRG2. Our results showed that NDRG2 may function as a tumor suppressor in CCRCC.
Ma
Jian-Jun
JJ
Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
Liao
Cheng-Gong
CG
Jiang
Xue
X
Zhao
Hua-Dong
HD
Yao
Li-Bo
LB
Bao
Ting-Yi
TY
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C466228:NDRG2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins