The Study On Expression Of Cancer-related Factors In Uterine Leiomyomas

Uterine leiomyomas are the most common pelvic benign tumors in women, occurring in women about35-50year of age. The incidence of leiomyomas is as high as51.2%-60%. Normal myometrium somatic mutations, the interaction between sex hormones and growth factors, oxidative stress, dysregulation of cell cycle and inflammation have been reported to be associated with the growth of leiomyomas. Clinical treatments of uterine leiomyomas include drug therapy of GnRHa and mifepristone, hysterectomy and myomectomy surgery.Thioredoxin (Trx) is an important regulator for maintaining redox balance. Trx has been reported to promote the growth, metastasis, invasion and infiltration of tumor cells, and inhibit apoptosis. Thioredoxin binding protein2(TBP-2) is a negative regulator of the biological function and expression of Trx. The down-regulation of TBP-2is associated with the formation of tumors and poor prognosis. The content of TBP-2in tumors is also related with the stage of cancer. Hypoxia-inducible factor-1a (HIF-1a) can increase the expression of vascular endothelial growth factor, and promote tumor angiogenesis. Forkheat protein3A (FOXO3A) is a transcription factor in regulating oxidative stress related gene expression. FOXO3A plays dual and opposing roles in the regulation of tumor growth. FOXO3A could act as a tumor suppressor gene. However, the knockdown of FOXO3A gene could inhibit tumor growth, this phenomenon is associated with FOXO3A resistence to oxidative stress. Heat shock protein70(Hsp70) is an important molecular chaperone that prevents protein aggregation and facilitates refolding of proteins. Hsp70can enhance the survival of tumor cells and inhibit the signal pathways of apoptosis and senescence. Cyclin D1is an important molecular for regulation cell proliferation. The dysregulation or over-expression of Cyclin D1would result in the cell proliferation and tumor formation. The Cyclin D1over-expression is also associated with the degree of malignancy and poor prognosis. Cyclooxygenase-2(Cox-2) is a key enzyme in mediating inflammatory responses. It is involved in the inflammation-mediated tumor angiogenesis. Cox-2is also related with the formation, proliferation, metastasis and invasion of tumors. Tumor necrosis factor-a (TNF-a) and IL-10have immunomodulatory effects that could participate in the regulation of tumor growth, apoptosis and invasion.In the present study, we examined the MDA level in leiomyomas and the matched normal myometrium using ELISA. And then the levels of Trx, Cyclin D1, FOXO3A, TBP-2, Hsp70, Cox-2, IL-10and TNF-α were examined in leiomyomas and the matched normal myometrium using Western blot and quantitive RT-PCR. Furthermore, we also explore the relation between these factor and pathogenesis of uterine leiomymas. In this study, we found that levels of Trx, HIF-1α, FOXO3A, Cyclin D1and Cox-2were increased in all leiomyomas examined, compared with the matched normal myometrium. In addition, IL-10and TNF-α were decreased in all leiomyomas examined, compared with the matched normal myometrium. However, the expression of TBP-2and Hsp70between leiomyomas and the matched normal myometrium has no difference.These results suggest that lipid peroxidation is associated with leiomymas and that Trx, HIF-1α, FOXO3A, Cyclin D1and Cox-2are involved in the pathogenesis of uterine leiomymas and are closely related to the uterine leiomyomas, TNF-α and IL-10are associated with the decline of immune function in uterine leiomyomas, however, TBP-2and Hsp70are not involved with the uterine leiomyomas.