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

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

doi:10.1186/1471-2407-8-303

Abstract

BackgroundNDRG2 (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.MethodsIn 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.ResultsThe 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.ConclusionOur 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.

Highlights

NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory
As human NDRG2 is important in cell proliferation and differentiation, we investigated whether NDRG2 participated in the carcinogenesis of thyroid cancer
Differential expression of Ndrg2 in thyroid carcinomas and normal tissues Because Ndrg2 expression is decreased in many types of cancer tissues [10,15], a preliminary analysis on Ndrg2 expression in thyroid tumors was performed using a tissue microarray

Summary

Introduction

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. NDRG2 mRNA was downregulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 exerts important functions in cell differentiation and tumor suppression. It remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Because Myc promotes cell proliferation and inhibits cell differentiation [7,8], most of the target genes that are transcriptionally repressed by Myc have the opposite biological role. They may inhibit cell proliferation, especially in cancer cells, or initiate cell differentiation

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Conclusion