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

Abstract

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.

Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins

“…Human mammary gland epithelial adenocarcinomas (MCF-7, MDA-MB-231, AU-565, and BT-483) and human normal mammary gland epithelial fibrocystic cell lines (MCF-10A, HBL-100) were obtained from the American Tissue Cell Culture collection (ATCC numbers HTB 22, HTB 26, CRL-2531, CRL 10317, HTB 131, and HTB121). All these cells were cultured according to our previous work [30]. Aqueous stock solutions of 10-lM Nic or NNK (Chemsyn, Lenexa, KS) were prepared in ddH 2 O.…”

“…RNA isolation and real-time quantitative PCR Total RNA was isolated using Trizol (Invitrogen, Carlsbad, CA), according to the manufacturer's protocol [30], from both human cell lines and breast tumor tissue samples that were acquired directly from patients. The a9-nAChR subunit and cyclin D3-specific primers were synthesized as described in a previous report [31] (Supplementary Table 1, available online).…”

Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells

“…ChIP assays using the cultured cells were performed as described previously [31]. In brief, after treatment of the cells with various doses of nicotine or E2 for varying periods, the cells were fixed with a final concentration of 1% formaldehyde by its direct addition to the cell culture media at 25°C for 15 min.…”

Identification of Novel Proteins Interacting with Vascular Endothelial Growth Inhibitor 174 in Renal Cell Carcinoma

“…Remarkably, accumulating evidence have suggested that ENO1 can function as an oncogenic protein by promoting cell proliferation, invasion and metastasis. ENO1 expression is frequently increased in diverse tumors, including head and neck, thyroid, breast, lung, prostate, colon and gastric cancer, glioma and cholangio carcinoma (46)(47)(48)(49). Moreover, overexpression of ENO1 is positively associated with progression and poor prognosis in several tumors (49).…”