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. However, the mechanisms of ERα effects on colorectal cancer cells remained un-clear. LoVo cells were transient transfected to overexpress ERα. It demonstrated that overexpressed ERα with or without E2 (10-8M) treatment could activate caspase-8, -9, and 3 and induce DNA fragmentation in LoVo cell. At the same time, overexpressed ERα plus E2 significantly increases the expression and promoter activity of hTNFa, and the DNA fragmentation effect induced by E2 plus ERα were reduced by the addition of hTNF antibody (0.1ng/ml). In addition, E2 plus ERα significantly upregulated p21 and p27 levels and downregulated the β-catenin and its target genes, cyclin D1 and Rb, which regulate the cell cycle and cell proliferation. The results indicate that E2 plus overexpressed ERα induce LoVo cell apoptosis might mediate through the increase of hTNFα gene expression, which in turn activate caspase-8, -9 and caspase-3 and lead to the DNA fragmentation and apoptosis. E2 plus ERα also showed the downregulation of β-catenin signalings implicating the suppression of proliferation and metastasis of colorectal cells. Efforts aiming at enhancing ERα expression and/or activity may be proved to be an alternative therapy against colorectal cancer.
