Uterine leiomyomas are benign tumors that develop from smooth muscle cells (SMCs). The reactive oxygen species (ROS) have been shown to be involved in the signaling pathways that stimulate proliferation of a variety of cell types. Thioredoxin-1 (TRX-1) is a redox-regulating protein, which is overexpressed in various tumors. In the present study, we investigated the expressions of TRX-1 and its related molecules in uterine leiomyomas and matched adjacent myometrium. Our results showed the expression of TRX-1 was increased in leiomyomas compared with the matched adjacent myometrium by quantitative RT-PCR and western blotting. FOXO3A expression was increased in leiomyomas compared with myometrium by western blotting. The mRNA levels of hypoxia-inducible factor-1α, cyclooxygenase-2 and cyclin D1 were increased in leiomyomas compared with the adjacent myometrium. The mRNA level of (thioredoxin-1-binding protein) TBP-2 in leiomyomas was not altered when compared with the matched adjacent myometrium. These results suggest that TRX-1 and some of its related molecules are associated with the pathogenesis of uterine leiomyomas. The identification of TRX-1 signaling pathways leading to cell proliferation points to another potential therapeutic target for treatment and/or prevention of uterine leiomyomas.
Keywords: cyclin D1; cyclooxygenase-2 (COX-2); hypoxia-inducible factor-1α (HIF-1α); thioredoxin-1 (TRX-1); uterine leiomyoma.