Apoptotic Effects of Over-Expressed Estrogen Receptor-β on LoVo Colon Cancer Cell is Mediated by p53 Signalings in a Ligand-Dependent Manner

Hsi-Hsien Hsu ； Sue-Fei Cheng ； Cheng-Chung Wu ； Chun-Hsien Chu ； Yi-Jiun Weng ； Chung-Sheng Lin ； Shin-Da Lee ； Hung-Chien Wu ； Chih-Yang Huang ； Wei-Wen Kuo

《The Chinese Journal of Physiology》 49卷2期 (2006/04) Pp. 110-116

並列摘要

Epidemiologic studies reported that the prevalence of hereditary non-polyposis colon cancer (HNPCC) in male is about 1.5-fold higher than that in female. Decreases in circulatory estradiol (E2) have been reported to downregulate the expression of E2 receptor (ER) and significantly increase the risk of colorectal cancer. Patients that received E2 replacement therapy were found to have a reduction in the incidence of colon adenoma and carcinoma. Furthermore, significant decreases in the expression of ER have been found in colorectal cancer specimens. These data strongly suggest the protective roles of E2 and ER against colorectal cancer. However, the mechanisms remain unexplored. LoVo cells were transient transfected to overexpress ER-β, DNA fragmentation and caspase activity assay were performed to evaluate apoptotic effects. Western blotting was used to evaluate protein levels, and luciferase activity assay to measure the TNF-α promoter activity. Our data clearly demonstrated that E2 and ER-β alone could upregulate p21 and p27 proteins, which further activate caspase-8 and caspase-9 to induce apoptosis in LoVo cell, and the ER-β effects were enhanced by E2. However, overexpressed ER-β did not influence the expression and promoter activity of TNF-α. In addition, E2 and overexpressed ER-β downregulated the β-catenin proteins which cause the downregulation of its target genes, cyclin D1 and Rb, to inhibit the cell cycle and cell proliferation. The results indicate that overexpressed ER-β may induce LoVo cell apoptosis and anti-proliferation by increasing p53 signaling in a ligand-dependent manner, and without hTNF-α involvement. Efforts aiming at enhancing ER-β expression and/or activity may prove to be an attractive alternative therapy against colorectal cancer.

並列關鍵字

estrogen receptor-β ； LoVo cells ； apoptotic effects ； antiproliferation

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