• 1. 沈陽軍區(qū)總醫(yī)院普通外科(遼寧沈陽 110016);;
  • 2. 第四軍醫(yī)大學(xué)基礎(chǔ)部生化與分子生物學(xué)教研室(陜西西安 710032);;
  • 3. 第四軍醫(yī)大學(xué)西京醫(yī)院肝膽外科(陜西西安 710032);

目的  探討NDRG2基因在人原發(fā)性肝細(xì)胞肝癌及正常肝組織中的表達(dá)及其臨床意義。
方法  收集原發(fā)性肝細(xì)胞肝癌及正常肝組織標(biāo)本,采用免疫組化ABC法、Western blot法及Real-time PCR法檢測原發(fā)性肝細(xì)胞肝癌及正常肝組織標(biāo)本中NDRG2蛋白和mRNA的表達(dá)情況,并結(jié)合圖像分析,比較兩者表達(dá)的差異。
結(jié)果  NDRG2蛋白在肝癌組織及正常肝組織中的表達(dá)陽性率分別為16.67%(5/30)和100%(30/30),2組差異有統(tǒng)計學(xué)意義(P<0.05),且陽性表達(dá)呈現(xiàn)在細(xì)胞質(zhì)中,細(xì)胞核中未見有表達(dá)。圖像分析結(jié)果顯示,NDRG2蛋白在肝癌組織中表達(dá)的相對含量為0.029 0±0.005 9,在正常肝組織中為0.109 2±0.002 8,前者低于后者,其差異具有統(tǒng)計學(xué)意義(P<0.05)。Western blot法檢測結(jié)果與免疫組化染色結(jié)果相一致,在肝癌組織及正常肝組織中均檢測到NDRG2蛋白,肝癌組織中NDRG2蛋白相對表達(dá)量為1.13±0.15,低于正常肝組織的1.57±0.18(P<0.05)。Real-time PCR分析結(jié)果顯示肝癌組織中NDRG2mRNA表達(dá)量為0.89±0.15,低于正常肝組織的1.48±0.17(P<0.05),但肝癌Edmondson-Steiner分級的各級肝癌組織之間NDRG2mRNA表達(dá)量差異均無統(tǒng)計學(xué)意義(P>0.05)。
結(jié)論  NDRG2基因在原發(fā)性肝細(xì)胞肝癌及正常肝組織中可能存在差異性表達(dá),提示該基因可能參與了肝細(xì)胞肝癌的發(fā)生和發(fā)展,但其具體作用及調(diào)控機(jī)理有待進(jìn)一步研究。

引用本文: 吳國強(qiáng),張健,李開宗,竇科峰,劉新平. NDRG2 基因在原發(fā)性肝細(xì)胞肝癌及正常肝組織中的表達(dá)研究. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(3): 266-270. doi: 復(fù)制

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. 陳杰, 張翊, 饒春明, 等. NDRG2 基因的克隆、表達(dá)及抑瘤活性研究 [J].中國生物制品學(xué)雜志,2004,17(4):200-203..
5. 張翊, 陳杰, 裴德寧, 等. 重組人蛋白對腫瘤細(xì)胞抑制作用研究 [J]. 中國腫瘤生物治療雜志, 2004, 11(3):204-207..
6. 胡曉蘭, 藥立波, 張遠(yuǎn)強(qiáng), 等.NDRG2 在人胚胎組織中的表達(dá)分布特點 [J].生理學(xué)報, 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. 吳國強(qiáng), 劉新平, 王立峰, 等. NDRG2 對肝癌細(xì)胞HepG2 凋亡的誘導(dǎo)作用 [J]. 細(xì)胞與分子免疫學(xué)雜志,2003, 19(4):357-360.
15. 吳國強(qiáng), 李開宗, 竇科峰, 等. 穩(wěn)定轉(zhuǎn)染NDRG2 基因?qū)θ烁伟┘?xì)胞HepG2 作用的觀察 [J].中華實驗外科, 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. 鄧艷春, 藥立波, 劉新平, 等. 人腦內(nèi)一含有ACP 樣結(jié)構(gòu)域新基因的發(fā)現(xiàn) [J]. 生物化學(xué)與生物物理進(jìn)展, 2001, 28(1):72-76..
18. 劉娜, 劉新平, 王立峰, 等. 抑癌候選基因NDRG2 在乳腺腫瘤組織及乳腺癌細(xì)胞系中的表達(dá)分析 [J]. 第四軍醫(yī)大學(xué)學(xué)報, 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. 張健, 陳蘇寧, 于江天, 等. 人NDRG2 啟動子的克隆與活性鑒定 [J]. 生物技術(shù)通訊, 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. 劉新平, 鄧艷春, 韓炯, 等. Ndrg2 基因表達(dá)對胃癌細(xì)胞增殖調(diào)控及其機(jī)理的研究 [J].生物化學(xué)與生物物理進(jìn)展, 2003,30(1):116-121..
26. 張翊, 裴德寧, 饒春明, 等. 質(zhì)粒介導(dǎo)的NDRG2 shRNA 抑制其在人腫瘤細(xì)胞HHCC 中表達(dá) [J]. 中國生物制品學(xué)雜志,2004, 17(5):267-269..
27. 裴德寧, 張翊, 饒春明, 等. 應(yīng)用shRNA 技術(shù)研究NDRG2在人胃癌細(xì)胞SGC7901 增殖中的作用 [J]. 藥物分析雜志,2008, 28(7):1021-1025..
  1. 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. 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. 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. 4. 陳杰, 張翊, 饒春明, 等. NDRG2 基因的克隆、表達(dá)及抑瘤活性研究 [J].中國生物制品學(xué)雜志,2004,17(4):200-203..
  5. 5. 張翊, 陳杰, 裴德寧, 等. 重組人蛋白對腫瘤細(xì)胞抑制作用研究 [J]. 中國腫瘤生物治療雜志, 2004, 11(3):204-207..
  6. 6. 胡曉蘭, 藥立波, 張遠(yuǎn)強(qiáng), 等.NDRG2 在人胚胎組織中的表達(dá)分布特點 [J].生理學(xué)報, 2006, 58(4):331-336..
  7. 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. 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. 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. 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. 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. 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. 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. 14. 吳國強(qiáng), 劉新平, 王立峰, 等. NDRG2 對肝癌細(xì)胞HepG2 凋亡的誘導(dǎo)作用 [J]. 細(xì)胞與分子免疫學(xué)雜志,2003, 19(4):357-360.
  15. 15. 吳國強(qiáng), 李開宗, 竇科峰, 等. 穩(wěn)定轉(zhuǎn)染NDRG2 基因?qū)θ烁伟┘?xì)胞HepG2 作用的觀察 [J].中華實驗外科, 2011, 28(12):2127-2130..
  16. 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. 17. 鄧艷春, 藥立波, 劉新平, 等. 人腦內(nèi)一含有ACP 樣結(jié)構(gòu)域新基因的發(fā)現(xiàn) [J]. 生物化學(xué)與生物物理進(jìn)展, 2001, 28(1):72-76..
  18. 18. 劉娜, 劉新平, 王立峰, 等. 抑癌候選基因NDRG2 在乳腺腫瘤組織及乳腺癌細(xì)胞系中的表達(dá)分析 [J]. 第四軍醫(yī)大學(xué)學(xué)報, 2004, 25(12):1065-1068.
  19. 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. 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. 21. 張健, 陳蘇寧, 于江天, 等. 人NDRG2 啟動子的克隆與活性鑒定 [J]. 生物技術(shù)通訊, 2007, 18(1):9-11..
  22. 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. 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. 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. 25. 劉新平, 鄧艷春, 韓炯, 等. Ndrg2 基因表達(dá)對胃癌細(xì)胞增殖調(diào)控及其機(jī)理的研究 [J].生物化學(xué)與生物物理進(jìn)展, 2003,30(1):116-121..
  26. 26. 張翊, 裴德寧, 饒春明, 等. 質(zhì)粒介導(dǎo)的NDRG2 shRNA 抑制其在人腫瘤細(xì)胞HHCC 中表達(dá) [J]. 中國生物制品學(xué)雜志,2004, 17(5):267-269..
  27. 27. 裴德寧, 張翊, 饒春明, 等. 應(yīng)用shRNA 技術(shù)研究NDRG2在人胃癌細(xì)胞SGC7901 增殖中的作用 [J]. 藥物分析雜志,2008, 28(7):1021-1025..