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KMID : 1134120070100030180
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Journal of Breast Cancer
2007 Volume.10 No. 3 p.180 ~ p.192
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A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer
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Park Kui-Sun
Jung Sung-Hoo
Youn Hyun-Jo
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Abstract
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Purpose: It is important to identify a potential tumor marker that is associated with pathophysiologic processes of breast cancer. N-Myc downstream regulated genes (NDRG) are composed of four subtypes (NDRG 1-4) and NDRG2 gene has been reported as a specifically expressed gene in the human solid tumor including breast cancer. Although NDRG2 inhibits cell proliferation and promote differentiation, the mo- lecular basis of the tumor-suppressor activity of NDRG2 in breast cancer is unknown. Herein, we tried to reveal the co- rrelations between the expression of NDRG2 and the various clinicopathologic prognostic factors and evaluate its func- tional and pathophysiological roles in tumorigenesis of breast cancer.
Method: We were obtained the 67 breast cancers and paired normal tissue samples from patients who operated for breast cancer between June 2002 and June 2004. The expression of NDRG2 were measured with immunohisto- chemistry using monoclonal antibody and it was used eu- karyotic transfection to manipulate the expression in MDA-MB-231 breast cancer cell line. Cell proliferation analysis were evaluated with trypan blue stain and status of differen- tially-expressed genes by NDRG2 overexpression were investigated with oligo microarray chip analysis.
Results: Significant difference of NDRG2 mRNA expression between breast cancer and normal tissue was not detected. However, NDRG2 was significantly down-regulated in breast cancer tissue, compared to normal tissue (p<0.0001). It was a inverse-correlation between the NDRG2 expression and tumor size, histologic grade although other clinicopatholo- gical parameters such as axillary lymph node metastasis were not correlated. Overexpression of NDRG2 in MDA-MB-231 cell showed a decrease of cell proliferation compared with Mock control. Of the 24,000 genes, 64 genes were in- creased in expression while 256 genes including cyclin D1 were repressed by NDRG2 overexpression.
Conclusions: Our results suggest that NDRG2 can function as a regulator of cell differentiation and cell cycle (as a tumor suppressor gene) in the early stage of breast cancer. In ad- dition, NDRG2 protein indicates a prognostic tumor marker for breast cancer.
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KEYWORD
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NDRG2, Breast cancer, MDA-MB-231 cell
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