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Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

Authors: Huadong Zhao, Jian Zhang, Jianguo Lu, Xianli He, Changsheng Chen, Xiaojun Li, Li Gong, Guoqiang Bao, Qiang Fu, Suning Chen, Wei Lin, Hai Shi, Jianjun Ma, Xinping Liu, Qingjiu Ma, Libo Yao

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid.

Methods

In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc.

Results

The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases.

Conclusion

Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.
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Literature
2.
go back to reference DePinho RA, Schreiber-Agus N, Alt FW: Myc family oncogenes in the development of normal and neoplastic cells. Adv Cancer Res. 1991, 57: 1-46.CrossRefPubMed DePinho RA, Schreiber-Agus N, Alt FW: Myc family oncogenes in the development of normal and neoplastic cells. Adv Cancer Res. 1991, 57: 1-46.CrossRefPubMed
4.
go back to reference Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature. 2004, 431: 1112-1117.CrossRefPubMed Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, Bachmann MH, Borowsky AD, Ruebner B, Cardiff RD, Yang Q, Bishop JM, Contag CH, Felsher DW: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature. 2004, 431: 1112-1117.CrossRefPubMed
5.
go back to reference Nesbit CE, Tersak JM, Prochownik EV: MYC oncogenes and human neoplastic disease. Oncogene. 1999, 18: 3004-3016.CrossRefPubMed Nesbit CE, Tersak JM, Prochownik EV: MYC oncogenes and human neoplastic disease. Oncogene. 1999, 18: 3004-3016.CrossRefPubMed
6.
go back to reference Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D: Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. New England Journal of Medicine. 1985, 313: 1111-1116.CrossRefPubMed Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D: Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. New England Journal of Medicine. 1985, 313: 1111-1116.CrossRefPubMed
7.
go back to reference Evan Gerard, Vousden Karen: Proliferation, cell cycle and apoptosis in cancer. Nature. 2001, 411: 342-348.CrossRefPubMed Evan Gerard, Vousden Karen: Proliferation, cell cycle and apoptosis in cancer. Nature. 2001, 411: 342-348.CrossRefPubMed
9.
go back to reference Kokame K, Kato H, Miyata T: Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis: GRP78/BiP and novel genes. J Biol Chem. 1996, 271: 29659-29665.CrossRefPubMed Kokame K, Kato H, Miyata T: Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis: GRP78/BiP and novel genes. J Biol Chem. 1996, 271: 29659-29665.CrossRefPubMed
10.
go back to reference Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC: N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer. 2003, 106: 342-347.CrossRefPubMed Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC: N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer. 2003, 106: 342-347.CrossRefPubMed
11.
go back to reference Qu X, Zhai Y, Wei H, Zhang C, Xing G, Yu Y, He F: Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biol. 2002, 2291–2: 35-44. Qu X, Zhai Y, Wei H, Zhang C, Xing G, Yu Y, He F: Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biol. 2002, 2291–2: 35-44.
12.
go back to reference Zhao W, Tang R, Huang Y: Cloning and expression pattern of the human NDRG 3 gene. Biochim Biophys Acta. 2001, 1519: 134-138.CrossRefPubMed Zhao W, Tang R, Huang Y: Cloning and expression pattern of the human NDRG 3 gene. Biochim Biophys Acta. 2001, 1519: 134-138.CrossRefPubMed
13.
go back to reference Kovacevic Z, Richardson DR: The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. Carcinogenesis. 2006, 2712: 2355-2366.CrossRef Kovacevic Z, Richardson DR: The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. Carcinogenesis. 2006, 2712: 2355-2366.CrossRef
14.
go back to reference Zhang J, Li F, Liu X, 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.CrossRefPubMed Zhang J, Li F, Liu X, 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.CrossRefPubMed
15.
go back to reference Lusis Eriks, Watson Mark, Chicoine Michael, Lyman Meghan, Roerig Peter, Reifenberger Guido, Gutmann David, Perry Arie: Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Research. 2005, 65: 7121-7126.CrossRefPubMed Lusis Eriks, Watson Mark, Chicoine Michael, Lyman Meghan, Roerig Peter, Reifenberger Guido, Gutmann David, Perry Arie: Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Research. 2005, 65: 7121-7126.CrossRefPubMed
16.
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
17.
go back to reference Lorentzen A, Vogel LK, Lewinsky RH, Saebø M, Skjelbred CF, Godiksen S, Hoff G, Tveit KM, Lothe IM, Ikdahl T, Kure EH, Mitchelmore C: Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma. BMC Cancer. 2007, 7: 192-CrossRefPubMedPubMedCentral Lorentzen A, Vogel LK, Lewinsky RH, Saebø M, Skjelbred CF, Godiksen S, Hoff G, Tveit KM, Lothe IM, Ikdahl T, Kure EH, Mitchelmore C: Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma. BMC Cancer. 2007, 7: 192-CrossRefPubMedPubMedCentral
18.
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.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.CrossRefPubMed
19.
go back to reference Choi SC, Kim KD, Kim JT: Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS Lett. 2003, 553: 413-418.CrossRefPubMed Choi SC, Kim KD, Kim JT: Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the differentiation of dendritic cells. FEBS Lett. 2003, 553: 413-418.CrossRefPubMed
20.
go back to reference Kondo T, Ezzat S, Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006, 6: 292-306.CrossRefPubMed Kondo T, Ezzat S, Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006, 6: 292-306.CrossRefPubMed
21.
go back to reference Malloy KM, Cunnane MF: Pathology and cytologic features of thyroid neoplasms. Surg Oncol Clin N Am. 2008, 17: 57-70.CrossRefPubMed Malloy KM, Cunnane MF: Pathology and cytologic features of thyroid neoplasms. Surg Oncol Clin N Am. 2008, 17: 57-70.CrossRefPubMed
22.
go back to reference Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B: bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 1995, 55: 237-241.PubMed Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B: bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 1995, 55: 237-241.PubMed
23.
go back to reference Hu XL, Liu XP, Deng YC, Lin SX, Wu L, Zhang J, Wang LF, Wang XB, Li X, Shen L, Zhang YQ, Yao LB: Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell Tissue Res. 2006, 325: 67-76.CrossRefPubMed Hu XL, Liu XP, Deng YC, Lin SX, Wu L, Zhang J, Wang LF, Wang XB, Li X, Shen L, Zhang YQ, Yao LB: Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell Tissue Res. 2006, 325: 67-76.CrossRefPubMed
24.
go back to reference Davies L, Welch HG: Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006, 295: 2164-2167.CrossRefPubMed Davies L, Welch HG: Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006, 295: 2164-2167.CrossRefPubMed
25.
go back to reference Park KS, Youn HJ, Jung SH: A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer. J Korean Breast Cancer Soc. 2007, 10: 180-192.CrossRef Park KS, Youn HJ, Jung SH: A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer. J Korean Breast Cancer Soc. 2007, 10: 180-192.CrossRef
26.
go back to reference Choi SC, Yoon SR, Park YP, Song EY, Kim JW, Kim WH, Yang Y, Lim JS, Lee HG: Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death. Exp Mol Med. 2007, 39: 705-14.CrossRefPubMed Choi SC, Yoon SR, Park YP, Song EY, Kim JW, Kim WH, Yang Y, Lim JS, Lee HG: Expression of NDRG2 is related to tumor progression and survival of gastric cancer patients through Fas-mediated cell death. Exp Mol Med. 2007, 39: 705-14.CrossRefPubMed
Metadata
Title
Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer
Authors
Huadong Zhao
Jian Zhang
Jianguo Lu
Xianli He
Changsheng Chen
Xiaojun Li
Li Gong
Guoqiang Bao
Qiang Fu
Suning Chen
Wei Lin
Hai Shi
Jianjun Ma
Xinping Liu
Qingjiu Ma
Libo Yao
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-303

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