Estrogen stimulates the expression of mismatch repair gene hMLH1 in colonic epithelial cells.

Estrogen is reported to have a protective effect on colon cancer; however, the underlying mechanism is unclear. Impaired mismatch repair plays an important role in colonic carcinogenesis. The purpose of this study was to investigate the association of estrogen on regulating mismatch repair expression in colonic epithelial cells. In cultured COLO205 cells, the effect of estradiol (E2) and antagonist ICI182.780 on the expression of hMLH1 and hMSH2 was studied using reverse transcription-PCR and Western blotting. The correlation between serum level E2 and the expression of hMLH1 and hMSH2 in colonic mucosal tissue of 42 healthy individuals was also examined using reverse transcription-PCR and immunohistochemical staining. E2 increased the expression of hMLH1 in COLO205 cells, which was suppressed by ICI182.780. However, the effect of E2 on hMSH2 expression was not significant in COLO205 cells. In healthy individuals, a strong positive correlation of E2 level with hMLH1 expression in normal colonic epithelial cell was observed when serum E2 level was >45 pg/mL, but no correlation was seen between E2 and hMSH2 expression. E2 affects the expression of hMLH1 but not hMSH2 in vitro, and high serum E2 level correlates with hMLH1 expression in vivo. These findings suggest that the anticolonic cancer effect of estrogen may be related to hMLH1 regulation.