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Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

Authors: Anders Lorentzen, Lotte K Vogel, Rikke H Lewinsky, Mona Sæbø, Camilla F Skjelbred, Sine Godiksen, Geir Hoff, Kjell M Tveit, Inger Marie Bowitz Lothe, Tone Ikdahl, Elin H Kure, Cathy Mitchelmore

Published in: BMC Cancer | Issue 1/2007

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Abstract

Background

It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis.

Methods

Using quantitative RT-PCR, we have determined the mRNA levels for NDRG2 in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). NDRG2 levels were normalised to β-actin.

Results

NDRG2 mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, NDRG2 expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for NDRG2 levels to decrease with increasing Dukes' stage (p < 0.05).

Conclusion

Our results demonstrate that expression of NDRG2 is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether NDRG2 down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.
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Literature
2.
go back to reference Shaw E, Mccue LA, Lawrence CE, Dordick JS: Identification of a novel class in the alpha/beta hydrolase fold superfamily: The N-myc differentiation-related proteins. Proteins. 2002, 47: 163-168. 10.1002/prot.10083.CrossRefPubMed Shaw E, Mccue LA, Lawrence CE, Dordick JS: Identification of a novel class in the alpha/beta hydrolase fold superfamily: The N-myc differentiation-related proteins. Proteins. 2002, 47: 163-168. 10.1002/prot.10083.CrossRefPubMed
3.
go back to reference Shimono A, Okuda T, Kondoh H: N-myc-dependent repression of Ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Mech Dev. 1999, 83: 39-52. 10.1016/S0925-4773(99)00025-8.CrossRefPubMed Shimono A, Okuda T, Kondoh H: N-myc-dependent repression of Ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Mech Dev. 1999, 83: 39-52. 10.1016/S0925-4773(99)00025-8.CrossRefPubMed
4.
go back to reference Deng YC, Yao LB, Chau L, Ng SSM, Peng Y, Liu XP, Au WS, Wang JC, Li FY, Ji SP, Han H, Nie XY, Li Q, Kung HF, Leung SY, Lin MCM: N-myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer. 2003, 106: 342-347. 10.1002/ijc.11228.CrossRefPubMed Deng YC, Yao LB, Chau L, Ng SSM, Peng Y, Liu XP, Au WS, Wang JC, Li FY, Ji SP, Han H, Nie XY, Li Q, Kung HF, Leung SY, Lin MCM: N-myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer. 2003, 106: 342-347. 10.1002/ijc.11228.CrossRefPubMed
5.
go back to reference Qu XH, Zhai Y, Wei HD, Zhang CG, Xing GC, Yu YT, He FC: Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biochem. 2002, 229: 35-44. 10.1023/A:1017934810825.CrossRefPubMed Qu XH, Zhai Y, Wei HD, Zhang CG, Xing GC, Yu YT, He FC: Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biochem. 2002, 229: 35-44. 10.1023/A:1017934810825.CrossRefPubMed
6.
go back to reference Mitchelmore C, Buchmann-Moller S, Rask L, West MJ, Troncoso JC, Jensen NA: NDRG2: a novel Alzheimer's disease associated protein. Neurobiol Dis. 2004, 16: 48-58. 10.1016/j.nbd.2004.01.003.CrossRefPubMed Mitchelmore C, Buchmann-Moller S, Rask L, West MJ, Troncoso JC, Jensen NA: NDRG2: a novel Alzheimer's disease associated protein. Neurobiol Dis. 2004, 16: 48-58. 10.1016/j.nbd.2004.01.003.CrossRefPubMed
7.
go back to reference Choi SC, Kim KD, Kim JT, Kim JW, Yoon DY, Choe YK, Chang YS, Paik SG, Lim JS: Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS Lett. 2003, 553: 413-418. 10.1016/S0014-5793(03)01030-5.CrossRefPubMed Choi SC, Kim KD, Kim JT, Kim JW, Yoon DY, Choe YK, Chang YS, Paik SG, Lim JS: Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS Lett. 2003, 553: 413-418. 10.1016/S0014-5793(03)01030-5.CrossRefPubMed
8.
go back to reference Zhang J, Li F, Liu X, Shen L, Liu J, Su J, Zhang W, Deng Y, Wang L, Liu N, Han W, Zhang J, Ji S, Yang A, Han H, Yao L: The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. J Biol Chem. 2006, 281: 39159-39168. 10.1074/jbc.M605820200.CrossRefPubMed Zhang J, Li F, Liu X, Shen L, Liu J, Su J, Zhang W, Deng Y, Wang L, Liu N, Han W, Zhang J, Ji S, Yang A, Han H, Yao L: The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. J Biol Chem. 2006, 281: 39159-39168. 10.1074/jbc.M605820200.CrossRefPubMed
9.
go back to reference Hummerich L, Muller R, Hess J, Kokocinski F, Hahn M, Furstenberger G, Mauch C, Lichter P, Angel P: Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. Oncogene. 2006, 25: 111-121.PubMed Hummerich L, Muller R, Hess J, Kokocinski F, Hahn M, Furstenberger G, Mauch C, Lichter P, Angel P: Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. Oncogene. 2006, 25: 111-121.PubMed
10.
go back to reference Lusis EA, Watson MA, Chicoine MR, Lyman M, Roerig P, Reifenberger G, Gutmann DH, Perry A: Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Research. 2005, 65: 7121-7126. 10.1158/0008-5472.CAN-05-0043.CrossRefPubMed Lusis EA, Watson MA, Chicoine MR, Lyman M, Roerig P, Reifenberger G, Gutmann DH, Perry A: Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Research. 2005, 65: 7121-7126. 10.1158/0008-5472.CAN-05-0043.CrossRefPubMed
11.
go back to reference Hu XL, Liu XP, Lin SX, Deng YC, Liu N, Li X, Yao LB: NDRG2 expression and mutation in human liver and pancreatic cancers. World J Gastroenterol. 2004, 10: 3518-3521.CrossRefPubMedPubMedCentral Hu XL, Liu XP, Lin SX, Deng YC, Liu N, Li X, Yao LB: NDRG2 expression and mutation in human liver and pancreatic cancers. World J Gastroenterol. 2004, 10: 3518-3521.CrossRefPubMedPubMedCentral
12.
go back to reference Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K: Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006, 9: 157-173. 10.1016/j.ccr.2006.02.019.CrossRefPubMed Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K: Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006, 9: 157-173. 10.1016/j.ccr.2006.02.019.CrossRefPubMed
13.
go back to reference Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G: The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol. 2003, 38: 635-642. 10.1080/00365520310003002.CrossRefPubMed Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G: The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol. 2003, 38: 635-642. 10.1080/00365520310003002.CrossRefPubMed
15.
go back to reference Johnson MR, Wang K, Smith JB, Heslin MJ, Diasio RB: Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal Biochem. 2000, 278: 175-184. 10.1006/abio.1999.4461.CrossRefPubMed Johnson MR, Wang K, Smith JB, Heslin MJ, Diasio RB: Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal Biochem. 2000, 278: 175-184. 10.1006/abio.1999.4461.CrossRefPubMed
17.
go back to reference Sugai T, Habano W, Jiao YF, Tsukahara M, Takeda Y, Otsuka K, Nakamura S: Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn. 2006, 8: 193-201. 10.2353/jmoldx.2006.050052.CrossRefPubMedPubMedCentral Sugai T, Habano W, Jiao YF, Tsukahara M, Takeda Y, Otsuka K, Nakamura S: Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn. 2006, 8: 193-201. 10.2353/jmoldx.2006.050052.CrossRefPubMedPubMedCentral
18.
go back to reference Nesbit CE, Tersak JM, Prochownik EV: MYC oncogenes and human neoplastic disease. Oncogene. 1999, 18: 3004-3016. 10.1038/sj.onc.1202746.CrossRefPubMed Nesbit CE, Tersak JM, Prochownik EV: MYC oncogenes and human neoplastic disease. Oncogene. 1999, 18: 3004-3016. 10.1038/sj.onc.1202746.CrossRefPubMed
19.
go back to reference Behrens J: The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochem Soc Trans. 2005, 33: 672-675. 10.1042/BST0330672.CrossRefPubMed Behrens J: The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochem Soc Trans. 2005, 33: 672-675. 10.1042/BST0330672.CrossRefPubMed
Metadata
Title
Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma
Authors
Anders Lorentzen
Lotte K Vogel
Rikke H Lewinsky
Mona Sæbø
Camilla F Skjelbred
Sine Godiksen
Geir Hoff
Kjell M Tveit
Inger Marie Bowitz Lothe
Tone Ikdahl
Elin H Kure
Cathy Mitchelmore
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-192

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