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    題名: Increased expression of enolase  in human breast cancer confers tamoxifen resistance in human breast cancer cells
    作者: 何元順
    Shih-Hsin Tu;Chih-Chiang Chang;Ching-Shyang Chen;Ka-Wai Tam;Ying-Jan Wang;Chia-Hwa Lee;Hsiao-Wei LinTzu-Chun Cheng3;Ching-Shui Huang1;2;Jan-Show Chu6;Neng-Yao Shih7;Li-C
    貢獻者: 醫學檢驗暨生物技術學系
    關鍵詞: Tamoxifen;Breast cancer;Enolase-1;Estrogen receptor alpha;Nuclear factor kappa B
    日期: 2009
    上傳時間: 2009-08-25 10:38:29 (UTC+8)
    摘要: Enolase-alpha (ENO-1) is a key glycolytic enzyme that has been used as a diagnostic marker to identify human lung cancers. To investigate the role of ENO-1 in breast cancer diagnosis and therapy, the mRNA levels of ENO-1 in 244 tumor and normal paired tissue samples and 20 laser capture-microdissected cell clusters were examined by quantitative real-time PCR analysis. Increased ENO-1 mRNA expression was preferentially detected in estrogen receptor-positive (ER+) tumors (tumor/normal ratio >90-fold) when compared to ER-negative (tumor/normal ratio >20-fold) tumor tissues. The data presented here demonstrate that those patients whose tumors highly expressed ENO-1 had a poor prognosis with greater tumor size (>2 cm, *P = .017), poor nodal status (N > 3, *P = .018), and a shorter disease-free interval (<==1 year, *P < .009). We also found that higher-expressing ENO-1 tumors confer longer distance relapse (tumor/normal ratio = 82.8-92.4-fold) when compared to locoregional relapse (tumor/normal ratio = 43.4-fold) in postsurgical 4-hydroxy-tamoxifen (4-OHT)-treated ER+ patients (*P = .014). These data imply that changes in tumor ENO-1 levels are related to clinical 4-OHT therapeutic outcome. In vitro studies demonstrated that decreasing ENO-1 expression using small interfering RNA (siRNA) significantly augmented 4-OHT (100 nM)-induced cytotoxicity in tamoxifen-resistant (Tam-R) breast cancer cells. These results suggest that downregulation of ENO-1 could be utilized as a novel pharmacological approach for overcoming 4-OHT resistance in breast cancer therapy.
    關聯: Breast Cancer Research and Treatment.
    資料類型: article
    顯示於類別:[醫學檢驗暨生物技術學系所] 期刊論文

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