Byoung Kil Lee

Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma.

Recently, it has been reported that SIRT1 and DBC1 may be involved in the development of tumors and predict poor survival in some cancers. However, their exact role is not clear. Therefore, we investigated the expression status and clinical significance of DBC1 and SIRT1 expression in breast carcinomas. We evaluated the immunohistochemical expression of DBC1, SIRT1, and p53 using a 3-mm core from 122 patients with breast cancer for tissue microarray. Positive expression of DBC1 and SIRT1 were seen in 71% and 67% of patients, respectively. In the patients with breast cancer, overall, expression of DBC1 and SIRT1 was significantly associated with distant metastatic relapse and shorter relapse-free survival and overall survival by univariate analysis. Tumor stage and DBC1 and SIRT1 expression were also independent prognostic factors by multivariate analysis. Among the patients who had received chemotherapy, DBC1 and SIRT1 expression was significantly associated with distant metastatic relapse and shorter survival by univariate analysis. DBC1 expression was also associated with distant metastatic relapse and shorter survival in patients who had received endocrine therapy, according to univariate and multivariate analysis. In conclusion, this study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for breast carcinoma patients.

Silibinin Enhances Ultraviolet B-Induced Apoptosis in MCF-7 Human Breast Cancer Cells

Purpose Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis. Methods The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry. Results A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells. Conclusion Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.

Clinical Outcome of Magnetic Resonance Imaging-Detected Additional Lesions in Breast Cancer Patients

Purpose The aim of this study was to investigate the clinical outcome of additional breast lesions identified with breast magnetic resonance imaging (MRI) in breast cancer patients. Methods A total of 153 patients who underwent breast MRI between July 2006 and March 2008 were retrospectively reviewed. Thirty-three patients (21.6&) were recommended for second-look ultrasound (US) for further characterization of additional lesions detected on breast MRI and these patients constituted our study population. Results Assessment for lesions detected on breast MRI consisted of the following: 25 benign lesions (73.5&), two indeterminate (5.9%), and seven malignant (20.6%) in 33 patients. Second-look US identified 12 additional lesions in 34 lesions (35.3%) and these lesions were confirmed by histological examination. Of the 12 lesions found in the 11 patients, six (50.0%) including one contralateral breast cancer were malignant. The surgical plan was altered in 18.2% (six of 33) of the patients. The use of breast MRI justified a change in treatment for four patients (66.7%) and caused two patients (33.3&) to undergo unwarranted additional surgical procedures. Conclusion Breast MRI identified additional multifocal or contralateral cancer which was not detected initially on conventional imaging in breast cancer patients. Breast MRI has become an indispensable modality in conjunction with conventional modalities for preoperative evaluation of patients with operable breast cancer.

NDRG2 correlated with favorable recurrence-free survival inhibits metastasis of mouse breast cancer cells via attenuation of active TGF-β production

N-myc downstream-regulated gene 2 (NDRG2) has been studied for its inhibitory effects against growth and metastasis of many tumor cell types. In this study, we showed NDRG2 expression was correlated with favorable recurrence-free survival of patients with breast cancer and inhibited metastasis of breast cancer cells (4T1). NDRG2 expression was examined in 189 breast carcinoma tissues and paired normal breast tissues using immunohistochemistry. Histological and clinicopathological data were correlated using Pearsons chi-square test of independence. NDRG2 expression in human breast cancer tissues was inversely associated with lymph node metastasis and pTNM stage. Furthermore, patients with breast cancer with a high level of NDRG2 expression showed favorable recurrence-free survival (P = 0.038). To study the effect of NDRG2 on metastasis in vivo, we established an NDRG2-overexpressing mouse breast cancer cell line (4T1-NDRG2) and measured the metastasis and survival of 4T1-NDRG2 tumor-bearing mice. To test whether transforming growth factor β (TGF-β)- mediated metastasis of 4T1 was inhibited by NDRG2 expression, TGF-Smad-binding element (SBE)-luciferase activity and/or measurement of active TGF-β were performed in cell or tumor tissue level. 4T1-NDRG2 cells grew gradually and showed less metastatic activity in vivo and low invasiveness in vitro. 4T1-NDRG2 cells showed lower SBE-luciferase activity and lower level of active autocrine TGF-β than 4T1-Mock did. Correctly, our data show that NDRG2 significantly suppress tumor metastasis by attenuating active autocrine TGF-β production, and the attenuation might be typically associated with the favorable recurrence-free survival of patients clinically.

Epigallocatechin gallate inhibits the growth of MDA‑MB‑231 breast cancer cells via inactivation of the β‑catenin signaling pathway

Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. β-catenin signaling modulators could be useful in the prevention and therapy of breast cancer. However, the precise anticancer effect of EGCG through the β-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between β-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on β-catenin expression in breast cancer cells. β-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. All patients were females diagnosed with invasive ductal carcinoma. Western blot analysis revealed that β-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. β-catenin expression was associated with lymph node metastasis (P=0.04), tumor-node-metastasis stage (P=0.03) and estrogen receptor status (P<0.01). EGCG decreased MDA-MB-231 cell viability and significantly downregulated the expression of β-catenin, phosphorylated Akt and cyclin D1. Remarkably, additive effects of LY294002 and wortmannin, two phosphatidylinositol-3 kinase inhibitors, were observed. The present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway. Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.