Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 121, Issue 3, Pages 539-553Publisher
SPRINGER
DOI: 10.1007/s10549-009-0492-0
Keywords
Tamoxifen; Breast cancer; Enolase-1; Estrogen receptor alpha; Nuclear factor kappa B
Categories
Funding
- National Science Council [NSC 95-2320-B-038-016-MY3, NSC 96-2314-B-038-002]
- Cathay Medical Center [95CGH-TMU-09, 96CGH-TMU-05]
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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 (a parts per thousand broken vertical bar 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.
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