Abstract
PURPOSE: Both obesity and gender are important etiological factors in renal cell carcinoma (RCC) development, suggesting a pivotal role of sex hormone signaling pathway and insulin-like growth factor (IGF) family in RCC carcinogenesis. Here, we aimed to investigate the effect of estrogen on RCC growth and the possible interaction between estrogen/estrogen receptor (ER) signaling pathway and the IGF axis. METHODS: ER-α and ER-β were detected in four human RCC cell lines. Cells were treated with 17β-estradiol (E2), and cell proliferation was determined using the cell counting kit-8 assay. Using siRNA, ER-β was downregulated in RCC cells and the effect of E2 on cell growth and IGF-1 receptor (IGF-1R) expression was examined. RESULTS: E2 inhibited 786-O cell but not A498 cell growth significantly. After the downregulation of ER-β, E2 showed no obvious inhibitory role in 786-O cells. E2 stimulation increased the expression of IGF-1R in 786-O cells. Downregulation of ER-β, as well as fulvestrant, attenuated the stimulatory effect of E2 on IGF-1R expression. CONCLUSION: Our results revealed that estrogen induced RCC growth inhibition via an ER-β-dependent pathway. Estrogen also upregulated the expression of IGF-1R, suggesting a link between estrogen/ER and IGF axis.