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 上傳時間:2009-08-25T02:38:29Z
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.
