A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer / 한국유방암학회지

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 molecular basis of the tumor-suppressor activity of NDRG2 in breast cancer is unknown. Herein, we tried to reveal the correlations between the expression of NDRG2 and the various clinicopathologic prognostic factors and evaluate its functional and pathophysiological roles in tumorigenesis of breast cancer. METHODS: 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 immunohistochemistry using monoclonal antibody and it was used eukaryotic 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 differentially-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 clinicopathological 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 increased in expression while 256 genes including cyclin D1 were repressed by NDRG2 overexpression. CONCLUSION: 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 addition, NDRG2 protein indicates a prognostic tumor marker for breast cancer.

A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer / 한국유방암학회지

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 molecular basis of the tumor-suppressor activity of NDRG2 in breast cancer is unknown. Herein, we tried to reveal the correlations between the expression of NDRG2 and the various clinicopathologic prognostic factors and evaluate its functional and pathophysiological roles in tumorigenesis of breast cancer. METHODS: 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 immunohistochemistry using monoclonal antibody and it was used eukaryotic 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 differentially-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 clinicopathological 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 increased in expression while 256 genes including cyclin D1 were repressed by NDRG2 overexpression. CONCLUSION: 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 addition, NDRG2 protein indicates a prognostic tumor marker for breast cancer.

Statin Reduced the Platelet CD63 and CD40L Expression in Atherosclerotic Ischemic Stroke with Hyperlipidemia

BACKGROUND: Statin (HMG-coA-reductase inhibitor) has been known to protect vessels from atherothrombosis through various mechanisms. In this study, we evaluated the effects of statin on reducing the platelet expressions of CD63 and CD40 ligand (CD40L) in subjects with atherosclerotic ischemic stroke. METHODS: Twenty-one patients (17 men, 4 women; mean age 59.0 +/- 10.2 years) with atherosclerotic ischemic stroke were recruited. They took simvastatin 20 mg per day for 90 days and discontinued for another 90 days. We studied the changes of platelet expressions of CD63 and CD40L in all the patients after the use and discontinuance of simvastatin using whole blood flow cytometry. RESULTS: After taking simvastatin 20mg for 90 days, the serum concentrations of LDL cholesterol decreased significantly (96.4 +/- 31.4 mg/dL, p<0.001) compared with those at the baseline (158.8 +/- 25.0 mg/dL). The platelet CD63 and C40L expressions were also significantly reduced by treatment of simvastatin 20 mg for 12 weeks (p<0.05). However, the effects of statin on CD63 and CD40L expressions disappeared after 12 weeks of cessation. Furthermore, changes of expressions of CD63 and CD40L by statin did not correlate with its cholesterol lowering effect (r=-0.311, p=0.386). CONCLUSIONS: This study demonstrates that the use of statin may be a helpful strategy to regulate the platelet activation in patients with atherosclerotic ischemic stroke.