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Effect of Ndrg2 Gene Expression on Gastric Carcinoma Cell Proliferation

LIU Xin- Ping, DENG Yan- Chun, HAN Jiong, LI Jian, WANG Ji- Cun, LI Ying, YAO Li- Bo ** (The Forth Military Medical University,Department of Biochemistry and Molecular Biology, Xian 710032, China)  
In previous study, a PCR- based subtractive hybridization method was used to isolate the human N- myc downstream regulated gene2 (Ndrg2) located at chromosome 14q11 2. Ndrg2 is low expressed in various tumor tissues. Ndrg2 tissue expression pattern suggests that its expression level is inversely related to cell proliferation rate. To investigate tumor suppressor activity of Ndrg2 gene, it was transiently transfected to an undifferentiated gastric mucos gland carcinoma cell line HGC- 27 which not expresses this gene itself confirmed by RT- PCR. It was found that the products of this gene may suppress the colony formation of gastric carcinoma cells in soft agar and induced apoptosis, as well as downregulated expression of cyclin D1 and cyclin E, but not affected cell cycle change in flowcytometry analysis. In addition, the antisense oligonucleotide of Ndrg2 gene was designed and added to the cultured differentiated gastric epidermal carcinoma cell line SGC- 7901 which expressed this gene itself confirmed by RT- PCR. It was observed that the numbers of colony formation of SGC- 7901 cell in soft agar decreased after Ndrg2 gene expression blocked by antisense oligonucleotide compared with sense oligonucleotide. In this case SGC- 7901 cell cycle was arrested in G1 phase. These results may be related to the low expression of cyclin D1 and cyclin E in gastric carcinoma cell line SGC- 7901. The results suggest that Ndrg2 gene may be of obviously key role in various differential stage gastric carcinoma cells.
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