Increased expression of enolase α in human breast cancer confers tamoxifen resistance in human breast cancer cells

Shih Hsin Tu, Chih Chiang Chang, Ching Shyang Chen, Ka Wai Tam, Ying Jan Wang, Chia Hwa Lee, Hsiao Wei Lin, Tzu Chun Cheng, Ching Shui Huang, Jan Show Chu, Neng Yao Shih, Li Ching Chen, Sy Jye Leu, Yuan Soon Ho, Chih Hsiung Wu

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Enolase-α (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 >90fold) 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 = 82.8-92.4fold) when compared to locoregional relapse (tumor/ normal ratio = 43.4-fold) in postsurgical 4-hydroxytamoxifen (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.

Original languageEnglish
Pages (from-to)539-553
Number of pages15
JournalBreast Cancer Research and Treatment
Volume121
Issue number3
DOIs
Publication statusPublished - 2010 Jun

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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