• 中國醫(yī)科大學(xué)附屬第一醫(yī)院乳腺外科（沈陽 110001）;

目的 綜合評述N-myc下游調(diào)節(jié)基因1（NDRG1）的作用以及該基因在腫瘤中的研究進(jìn)展情況。方法 收集近年來有關(guān)NDRG1作用及其與腫瘤關(guān)系的文獻(xiàn)并作綜述。結(jié)果 NDRG1在機(jī)體對組織缺氧的反應(yīng)、組織分化等方面發(fā)揮著重要作用，在腫瘤的形成以及侵襲和轉(zhuǎn)移中的作用尤為突出。結(jié)論 NDRG1可能是腫瘤轉(zhuǎn)移方面的一個候選相關(guān)基因，有望成為腫瘤的一個預(yù)后指標(biāo)。

引用本文： 馬薇,宋英杰,樊濤,吳云飛. NDRG1的作用及其在腫瘤中的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(12): 1326-1329. doi: 復(fù)制

1. van Belzen N, Dinjens WN, Diesveld MP, et al. A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms [J]. Lab Invest, 1997; 77(1): 85-92.
2. Kurdistani SK, Arizti P, Reimer CL, et al. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage [J]. Cancer Res, 1998; 58(19): 4439-4444.
3. Guan RJ, Ford HL, Fu Y, et al. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer [J]. Cancer Res, 2000; 60(3): 749-755.
4. Kokame K, Kato H, Miyata T. Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes [J]. J Biol Chem, 1996; 271(47): 29659-29665.
5. Zhou RH, Kokame K, Tsukamoto Y, et al. Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart [J]. Genomics, 2001; 73(1): 86-97.
6. Lachat P, Shaw P, Gebhard S, et al. Expression of NDRG1, a differentiation-related gene, in human tissues [J]. Histochem Cell Biol, 2002; 118(5): 399-408.
7. Piquemal D, Joulia D, Balaguer P, et al. Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells [J]. Biochim Biophys Acta, 1999; 1450(3): 364-373.
8. Gómez-Casero E, Navarro M, Rodríguez-Puebla ML, et al. Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis [J]. Mol Carcinog, 2001; 32(2): 100-109.
9. Angst E, Sibold S, Tiffon C, et al. Cellular differentiation determines the expression of the hypoxia-inducible protein NDRG1 in pancreatic cancer [J]. Br J Cancer, 2006; 95(3): 307-313.
10. 何靜, 周柔麗. NDRG1基因與肝組織分化及癌變的相關(guān)性 [J]. 北京大學(xué)學(xué)報(醫(yī)學(xué)版), 2003; 35(5): 471-475.
11. Kim KT, Ongusaha PP, Hong YK, et al. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint [J]. J Biol Chem, 2004; 279(37): 38597-38602.
12. Zhang P, Tchou-Wong KM, Costa M. Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter [J]. Cancer Res, 2007; 67(19): 9125-9133.
13. Sibold S, Roh V, Keogh A, et al. Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma [J]. FEBS Lett, 2007; 581(5): 989-994.
14. Cangul H. Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers [J]. BMC Genet, 2004; 5: 27.
15. Chen B, Nelson DM, Sadovsky Y. N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury [J]. J Biol Chem, 2006; 281(5): 2764-2772.
16. Kalaydjieva L, Gresham D, Gooding R, et al. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom [J]. Am J Hum Genet, 2000; 67(1): 47-58.
17. Okuda T, Higashi Y, Kokame K, et al. Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves [J]. Mol Cell Biol, 2004; 24(9): 3949-3956.
18. Ulrix W, Swinnen JV, Heyns W, et al. The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells [J]. FEBS Lett, 1999; 455(1-2): 23-26.
19. Tu LC, Yan X, Hood L, et al. Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells [J]. Mol Cell Proteomics, 2007; 6(4): 575-588.
20. Fotovati A, Fujii T, Yamaguchi M, et al. 17Beta-estradiol induces down-regulation of Cap43/NDRG1/Drg-1, a putative differentiation-related and metastasis suppressor gene, in human breast cancer cells [J]. Clin Cancer Res, 2006; 12(10): 3010-3018.
21. Stein S, Thomas EK, Herzog B, et al. NDRG1 is necessary for p53-dependent apoptosis [J].J Biol Chem, 2004; 279(47): 48930-48940.
22. Bandyopadhyay S, Pai SK, Hirota S, et al. PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer [J]. Cancer Res, 2004; 64(21): 7655-7660.
23. Chen J, Li S, Yang Z, et al. Correlation between NDRG1 and PTEN expression in endometrial carcinoma [J]. Cancer Sci, 2008; 99(4): 706-710.
24. Masuda K, Ono M, Okamoto M, et al. Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells [J]. Int J Cancer, 2003; 105(6): 803-810.
25. Taketomi Y, Sugiki T, Saito T, et al. Identification of NDRG1 as an early inducible gene during in vitro maturation of cultured mast cells [J]. Biochem Biophys Res Commun, 2003; 306(2): 339-346.
26. Agarwala KL, Kokame K, Kato H, et al. Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein [J]. Biochem Biophys Res Commun, 2000; 272(3): 641-647.
27. Kokame K, Kato H, Miyata T. Nonradioactive differential display cloning of genes induced by homocysteine in vascular endothelial cells [J]. Methods, 1998; 16(4): 434-443.
28. Wang Z, Wang F, Wang WQ, et al. Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm [J]. World J Gastroenterol, 2004; 10(4): 550-554.
29. 王震, 劉乾, 陳琦, 等. NDRG1基因與乳腺癌轉(zhuǎn)移的關(guān)系及其轉(zhuǎn)染對乳腺癌細(xì)胞株增殖及侵襲力的影響 [J]. 中華病理學(xué)雜志, 2006; 35(6): 333-338.
30. Nagai MA, Gerhard R, Fregnani JH, et al. Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients [J]. Breast Cancer Res Treat, 2010. [Epub ahead of print].
31. Bandyopadhyay S, Pai SK, Gross SC, et al. The Drg-1 gene suppresses tumor metastasis in prostate cancer [J]. Cancer Res, 2003; 63(8): 1731-1736.
32. Song Y, Oda Y, Hori M, et al. N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin [J]. Hum Pathol, 2010; 41(2): 214-222.
33. Maruyama Y, Ono M, Kawahara A, et al. Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis [J]. Cancer Res, 2006; 66(12): 6233-6242.
34. Ando T, Ishiguro H, Kimura M, et al. Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma [J]. Dis Esophagus, 2006; 19(6): 454-458.
35. Strzelczyk B, Szulc A, Rzepko R, et al. Identification of high-risk stage Ⅱ colorectal tumors by combined analysis of the NDRG1 gene expression and the depth of tumor invasion [J]. Ann Surg Oncol, 2009; 16(5): 1287-1294.
  1. 1. van Belzen N, Dinjens WN, Diesveld MP, et al. A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms [J]. Lab Invest, 1997; 77(1): 85-92.
  2. 2. Kurdistani SK, Arizti P, Reimer CL, et al. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage [J]. Cancer Res, 1998; 58(19): 4439-4444.
  3. 3. Guan RJ, Ford HL, Fu Y, et al. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer [J]. Cancer Res, 2000; 60(3): 749-755.
  4. 4. Kokame K, Kato H, Miyata T. Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes [J]. J Biol Chem, 1996; 271(47): 29659-29665.
  5. 5. Zhou RH, Kokame K, Tsukamoto Y, et al. Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart [J]. Genomics, 2001; 73(1): 86-97.
  6. 6. Lachat P, Shaw P, Gebhard S, et al. Expression of NDRG1, a differentiation-related gene, in human tissues [J]. Histochem Cell Biol, 2002; 118(5): 399-408.
  7. 7. Piquemal D, Joulia D, Balaguer P, et al. Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells [J]. Biochim Biophys Acta, 1999; 1450(3): 364-373.
  8. 8. Gómez-Casero E, Navarro M, Rodríguez-Puebla ML, et al. Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis [J]. Mol Carcinog, 2001; 32(2): 100-109.
  9. 9. Angst E, Sibold S, Tiffon C, et al. Cellular differentiation determines the expression of the hypoxia-inducible protein NDRG1 in pancreatic cancer [J]. Br J Cancer, 2006; 95(3): 307-313.
  10. 10. 何靜, 周柔麗. NDRG1基因與肝組織分化及癌變的相關(guān)性 [J]. 北京大學(xué)學(xué)報(醫(yī)學(xué)版), 2003; 35(5): 471-475.
  11. 11. Kim KT, Ongusaha PP, Hong YK, et al. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint [J]. J Biol Chem, 2004; 279(37): 38597-38602.
  12. 12. Zhang P, Tchou-Wong KM, Costa M. Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter [J]. Cancer Res, 2007; 67(19): 9125-9133.
  13. 13. Sibold S, Roh V, Keogh A, et al. Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma [J]. FEBS Lett, 2007; 581(5): 989-994.
  14. 14. Cangul H. Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers [J]. BMC Genet, 2004; 5: 27.
  15. 15. Chen B, Nelson DM, Sadovsky Y. N-myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury [J]. J Biol Chem, 2006; 281(5): 2764-2772.
  16. 16. Kalaydjieva L, Gresham D, Gooding R, et al. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom [J]. Am J Hum Genet, 2000; 67(1): 47-58.
  17. 17. Okuda T, Higashi Y, Kokame K, et al. Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves [J]. Mol Cell Biol, 2004; 24(9): 3949-3956.
  18. 18. Ulrix W, Swinnen JV, Heyns W, et al. The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells [J]. FEBS Lett, 1999; 455(1-2): 23-26.
  19. 19. Tu LC, Yan X, Hood L, et al. Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells [J]. Mol Cell Proteomics, 2007; 6(4): 575-588.
  20. 20. Fotovati A, Fujii T, Yamaguchi M, et al. 17Beta-estradiol induces down-regulation of Cap43/NDRG1/Drg-1, a putative differentiation-related and metastasis suppressor gene, in human breast cancer cells [J]. Clin Cancer Res, 2006; 12(10): 3010-3018.
  21. 21. Stein S, Thomas EK, Herzog B, et al. NDRG1 is necessary for p53-dependent apoptosis [J].J Biol Chem, 2004; 279(47): 48930-48940.
  22. 22. Bandyopadhyay S, Pai SK, Hirota S, et al. PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer [J]. Cancer Res, 2004; 64(21): 7655-7660.
  23. 23. Chen J, Li S, Yang Z, et al. Correlation between NDRG1 and PTEN expression in endometrial carcinoma [J]. Cancer Sci, 2008; 99(4): 706-710.
  24. 24. Masuda K, Ono M, Okamoto M, et al. Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells [J]. Int J Cancer, 2003; 105(6): 803-810.
  25. 25. Taketomi Y, Sugiki T, Saito T, et al. Identification of NDRG1 as an early inducible gene during in vitro maturation of cultured mast cells [J]. Biochem Biophys Res Commun, 2003; 306(2): 339-346.
  26. 26. Agarwala KL, Kokame K, Kato H, et al. Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein [J]. Biochem Biophys Res Commun, 2000; 272(3): 641-647.
  27. 27. Kokame K, Kato H, Miyata T. Nonradioactive differential display cloning of genes induced by homocysteine in vascular endothelial cells [J]. Methods, 1998; 16(4): 434-443.
  28. 28. Wang Z, Wang F, Wang WQ, et al. Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm [J]. World J Gastroenterol, 2004; 10(4): 550-554.
  29. 29. 王震, 劉乾, 陳琦, 等. NDRG1基因與乳腺癌轉(zhuǎn)移的關(guān)系及其轉(zhuǎn)染對乳腺癌細(xì)胞株增殖及侵襲力的影響 [J]. 中華病理學(xué)雜志, 2006; 35(6): 333-338.
  30. 30. Nagai MA, Gerhard R, Fregnani JH, et al. Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients [J]. Breast Cancer Res Treat, 2010. [Epub ahead of print].
  31. 31. Bandyopadhyay S, Pai SK, Gross SC, et al. The Drg-1 gene suppresses tumor metastasis in prostate cancer [J]. Cancer Res, 2003; 63(8): 1731-1736.
  32. 32. Song Y, Oda Y, Hori M, et al. N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin [J]. Hum Pathol, 2010; 41(2): 214-222.
  33. 33. Maruyama Y, Ono M, Kawahara A, et al. Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis [J]. Cancer Res, 2006; 66(12): 6233-6242.
  34. 34. Ando T, Ishiguro H, Kimura M, et al. Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma [J]. Dis Esophagus, 2006; 19(6): 454-458.
  35. 35. Strzelczyk B, Szulc A, Rzepko R, et al. Identification of high-risk stage Ⅱ colorectal tumors by combined analysis of the NDRG1 gene expression and the depth of tumor invasion [J]. Ann Surg Oncol, 2009; 16(5): 1287-1294.