The Expression and Significance of NDRG2 Gene in Primary Hepatocellular Carcinoma and Normal Hepatic Tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Guoqiang ¹ , ZHANG Jian ² , LI Kaizong ³ , DOU Kefeng ³ , LIU Xinping. ²

1.Department of General Surgery， The General Military Hospital of Shenyang Commanding Area， Shenyang 110016， Liaoning Province，China;;
2.Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an 710032,Shaanxi Province, China;;
3.Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University,Xi’an 710032, Shaanxi Province, China;

Corresponding author：

Keywords：

NDRG2 gene; Human primary hepatocellular carcinoma; Immunohistochemistry; Western blot; Real-time PCR

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Objective 　To explore the expression and function of NDRG2 gene in human primary hepatocellular carcinoma and normal hepatic tissues.
Methods 　The immunohistochemical ABC method， Western blot， and Real-time PCR were used to investigate the expression and content of NDRG2 in human hepatocellular carcinoma and hepatic normal biopsies.
Results 　The NDRG2 protein located in cytoplasm. The positive rate was 16.67%（5/30） and 100%（30/30） in hepatocellular carcinoma and normal hepatic tissues, respectively. The relative content of NDRG2 protein in hepatocellular carcinoma and normal hepatic tissues were 0.029 0±0.005 9 and 0.109 2±0.002 8. There were significant differences between human hepatocellular carcinoma and hepatic normal biopsies both in staining positive rates and relative content（P＜0.05）. The Western blot also agreed with the result，the expression level of NDRG2 protein in hepatocellular carcinoma and normal hepatic tissues was 1.13±0.15 and 1.57±0.18， respectively, there was significant difference（P＜0.05）. Also, compared with normal hepatic tissues, the expression level of NDRG2 mRNA in carcinoma tissues was reduced significantly (0.89±0.15 vs. 1.48±0.17, P＜0.05). However, there were no significant differences in NDRG2mRNA expression between Edmondson-Steiner grades.
Conclusions 　There possibly have difference in NDRG2 expression between human primary hepatocellular carcinoma and normal hepatic tissue. NDRG2 gene may take part in the pathogenesis of human primary hepatocellular carcinoma. Futher study will be needed to study its mechanism and function.

Citation： WU Guoqiang,ZHANG Jian,LI Kaizong,DOU Kefeng,LIU Xinping.. The Expression and Significance of NDRG2 Gene in Primary Hepatocellular Carcinoma and Normal Hepatic Tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(3): 266-270. doi: Copy

1.	Deng Y， Yao L， Chau L， et al. N-Myc downstream-regulated gene2 (NDRG2) inhibits glioblastoma cell proliferation [J]. Int J Cancer， 2003， 106(3)：342-347.
2.	Park MY， Choi SC， Lee HS， et al. A quantitative analysis of N-myc downstream regulated gene 2 (NDRG 2) in human tissues and cell lysates by reverse-phase protein microarray [J]. Clin Chim Acta， 2008， 387(1-2)： 84-89.
3.	Park Y， Shon SK， Kim A， et al. SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells [J]. Biochem Biophys Res Commun， 2007， 363(2)： 361-367.
4.	陈杰，张翊，饶春明，等. NDRG2 基因的克隆、表达及抑瘤活性研究 [J]．中国生物制品学杂志，2004，17(4)：200-203．.
5.	张翊，陈杰，裴德宁，等. 重组人蛋白对肿瘤细胞抑制作用研究 [J]. 中国肿瘤生物治疗杂志， 2004， 11(3)：204-207．.
6.	胡晓兰，药立波，张远强，等．NDRG2 在人胚胎组织中的表达分布特点 [J]．生理学报， 2006， 58(4)：331-336．.
7.	Zhang J， Liu J， Li X， et al. The physical and functional interaction of NDRG2 with MSP58 in cells [J]. Biochem Biophys Res Commun， 2007， 352(1)：6-11.
8.	Choi SC， Kim KD， Kim JT， et al. Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells [J]. FEBS Lett， 2003， 553(3)：413-418.
9.	Sheerazed B， Michel F， Maria-Christina Z， et al. Characterization of rat NDRG2 (N-Myc downstream regulated gene 2)， a novel early mineralocorticoid-specific induced gene [J]. J Biol Chem， 2002， 277(35)：31506-31515.
10.	Nichols NR. Ndrg2， a novel gene regulated by adrenal steroids and antidepressants， is highly expressed in astrocytes [J]. Ann N Y Acad Sci， 2003， 1007：349-356.
11.	Wang L， Liu N， Yao L， et al. NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells [J]. Cell Physiol Biochem， 2008， 21(1-3)：239-250.
12.	Choi SC， Kim KD， Kim JT， et al. Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity [J]. J Leukoc Biol，2008， 83(1)：89-98.
13.	Wielpütz MO， Lee IH， Dinudom A，et a1. (NDRG2) stimulates amiloride-sensitive Na+ currents in Xenopus laevis oocytes and fisher rat thyroid cells [J]. J Biol Chem， 2007， 282(38)：28264-28273.
14.	吴国强，刘新平，王立峰，等. NDRG2 对肝癌细胞HepG2 凋亡的诱导作用 [J]. 细胞与分子免疫学杂志，2003， 19(4)：357-360.
15.	吴国强，李开宗，窦科峰，等. 稳定转染NDRG2 基因对人肝癌细胞HepG2 作用的观察 [J]．中华实验外科， 2011， 28(12)：2127-2130．.
16.	Zhou L， Rui JA， Ye DX， et al. Edmondson-Steiner grading increases the predictive efficiency of TNM staging for long-term survival of patients with hepatocellular carcinoma after curative resection [J]. World J Surg， 2008， 32(8)：1748-1756.
17.	邓艳春，药立波，刘新平，等. 人脑内一含有ACP 样结构域新基因的发现 [J]. 生物化学与生物物理进展， 2001， 28(1)：72-76．.
18.	刘娜，刘新平，王立峰，等. 抑癌候选基因NDRG2 在乳腺肿瘤组织及乳腺癌细胞系中的表达分析 [J]. 第四军医大学学报， 2004， 25(12)：1065-1068.
19.	Lorentzen A， Vogel LK， Lewinsky RH， et al. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma [J]. BMC Cancer， 2007， 7：192.
20.	Lusis EA， Watson MA， Chicoine MR， et al. Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma [J].Cancer Res， 2005， 65(16)：7121-7126.
21.	张健，陈苏宁，于江天，等. 人NDRG2 启动子的克隆与活性鉴定 [J]. 生物技术通讯， 2007， 18(1)：9-11．.
22.	Boulkroun S， Le Moellic C， Blot-Chabaud M， et al. Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct [J]. Pflugers Arch， 2005， 451(2)：388-394.
23.	Svensson E， Vidovic K， Olofsson T， et al. The wilms’ tumor gene 1 (WT1) induces expression of the n-myc downstream regulated gene 2 (NDRG2) [J]. DNA Cell Biol， 2007， 26(8)：589-597.
24.	Burchfield JG， Lennard AJ， Narasimhan S， et al. Akt mediates insulin-stimulated phosphorylation of Ndrg2：evidence for cross-talk with protein kinase C theta [J]. J Biol Chem， 2004，279(18)： 18623-18632.
25.	刘新平，邓艳春，韩炯，等. Ndrg2 基因表达对胃癌细胞增殖调控及其机理的研究 [J]．生物化学与生物物理进展， 2003，30(1)：116-121．.
26.	张翊，裴德宁，饶春明，等. 质粒介导的NDRG2 shRNA 抑制其在人肿瘤细胞HHCC 中表达 [J]. 中国生物制品学杂志，2004， 17(5)：267-269．.
27.	裴德宁，张翊，饶春明，等. 应用shRNA 技术研究NDRG2在人胃癌细胞SGC7901 增殖中的作用 [J]. 药物分析杂志，2008， 28(7)：1021-1025．.

1. Deng Y， Yao L， Chau L， et al. N-Myc downstream-regulated gene2 (NDRG2) inhibits glioblastoma cell proliferation [J]. Int J Cancer， 2003， 106(3)：342-347.
2. Park MY， Choi SC， Lee HS， et al. A quantitative analysis of N-myc downstream regulated gene 2 (NDRG 2) in human tissues and cell lysates by reverse-phase protein microarray [J]. Clin Chim Acta， 2008， 387(1-2)： 84-89.
3. Park Y， Shon SK， Kim A， et al. SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells [J]. Biochem Biophys Res Commun， 2007， 363(2)： 361-367.
4. 陈杰，张翊，饶春明，等. NDRG2 基因的克隆、表达及抑瘤活性研究 [J]．中国生物制品学杂志，2004，17(4)：200-203．.
5. 张翊，陈杰，裴德宁，等. 重组人蛋白对肿瘤细胞抑制作用研究 [J]. 中国肿瘤生物治疗杂志， 2004， 11(3)：204-207．.
6. 胡晓兰，药立波，张远强，等．NDRG2 在人胚胎组织中的表达分布特点 [J]．生理学报， 2006， 58(4)：331-336．.
7. Zhang J， Liu J， Li X， et al. The physical and functional interaction of NDRG2 with MSP58 in cells [J]. Biochem Biophys Res Commun， 2007， 352(1)：6-11.
8. Choi SC， Kim KD， Kim JT， et al. Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells [J]. FEBS Lett， 2003， 553(3)：413-418.
9. Sheerazed B， Michel F， Maria-Christina Z， et al. Characterization of rat NDRG2 (N-Myc downstream regulated gene 2)， a novel early mineralocorticoid-specific induced gene [J]. J Biol Chem， 2002， 277(35)：31506-31515.
10. Nichols NR. Ndrg2， a novel gene regulated by adrenal steroids and antidepressants， is highly expressed in astrocytes [J]. Ann N Y Acad Sci， 2003， 1007：349-356.
11. Wang L， Liu N， Yao L， et al. NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells [J]. Cell Physiol Biochem， 2008， 21(1-3)：239-250.
12. Choi SC， Kim KD， Kim JT， et al. Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity [J]. J Leukoc Biol，2008， 83(1)：89-98.
13. Wielpütz MO， Lee IH， Dinudom A，et a1. (NDRG2) stimulates amiloride-sensitive Na+ currents in Xenopus laevis oocytes and fisher rat thyroid cells [J]. J Biol Chem， 2007， 282(38)：28264-28273.
14. 吴国强，刘新平，王立峰，等. NDRG2 对肝癌细胞HepG2 凋亡的诱导作用 [J]. 细胞与分子免疫学杂志，2003， 19(4)：357-360.
15. 吴国强，李开宗，窦科峰，等. 稳定转染NDRG2 基因对人肝癌细胞HepG2 作用的观察 [J]．中华实验外科， 2011， 28(12)：2127-2130．.
16. Zhou L， Rui JA， Ye DX， et al. Edmondson-Steiner grading increases the predictive efficiency of TNM staging for long-term survival of patients with hepatocellular carcinoma after curative resection [J]. World J Surg， 2008， 32(8)：1748-1756.
17. 邓艳春，药立波，刘新平，等. 人脑内一含有ACP 样结构域新基因的发现 [J]. 生物化学与生物物理进展， 2001， 28(1)：72-76．.
18. 刘娜，刘新平，王立峰，等. 抑癌候选基因NDRG2 在乳腺肿瘤组织及乳腺癌细胞系中的表达分析 [J]. 第四军医大学学报， 2004， 25(12)：1065-1068.
19. Lorentzen A， Vogel LK， Lewinsky RH， et al. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma [J]. BMC Cancer， 2007， 7：192.
20. Lusis EA， Watson MA， Chicoine MR， et al. Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma [J].Cancer Res， 2005， 65(16)：7121-7126.
21. 张健，陈苏宁，于江天，等. 人NDRG2 启动子的克隆与活性鉴定 [J]. 生物技术通讯， 2007， 18(1)：9-11．.
22. Boulkroun S， Le Moellic C， Blot-Chabaud M， et al. Expression of androgen receptor and androgen regulation of NDRG2 in the rat renal collecting duct [J]. Pflugers Arch， 2005， 451(2)：388-394.
23. Svensson E， Vidovic K， Olofsson T， et al. The wilms’ tumor gene 1 (WT1) induces expression of the n-myc downstream regulated gene 2 (NDRG2) [J]. DNA Cell Biol， 2007， 26(8)：589-597.
24. Burchfield JG， Lennard AJ， Narasimhan S， et al. Akt mediates insulin-stimulated phosphorylation of Ndrg2：evidence for cross-talk with protein kinase C theta [J]. J Biol Chem， 2004，279(18)： 18623-18632.
25. 刘新平，邓艳春，韩炯，等. Ndrg2 基因表达对胃癌细胞增殖调控及其机理的研究 [J]．生物化学与生物物理进展， 2003，30(1)：116-121．.
26. 张翊，裴德宁，饶春明，等. 质粒介导的NDRG2 shRNA 抑制其在人肿瘤细胞HHCC 中表达 [J]. 中国生物制品学杂志，2004， 17(5)：267-269．.
27. 裴德宁，张翊，饶春明，等. 应用shRNA 技术研究NDRG2在人胃癌细胞SGC7901 增殖中的作用 [J]. 药物分析杂志，2008， 28(7)：1021-1025．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Expression and Significance of NDRG2 Gene in Primary Hepatocellular Carcinoma and Normal Hepatic Tissues

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