Estrogen affects cell growth and IGF-1 receptor expression in renal cell carcinoma

Abstract

PurposeBoth 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.MethodsER-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.ResultsE2 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.ConclusionOur 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.

Oral intake of royal jelly improves anti‑cancer effects and suppresses adverse events of molecular targeted therapy by regulating TNF‑α and TGF‑β in renal cell carcinoma: A preliminary study based on a randomized double‑blind clinical trial

“…Several in vivo and in vitro studies have demonstrated that TNF-α levels correlate with risk of cancer, tumor growth, invasion, and metastasis of RCC (18,21,30). Furthermore, various anti-cancer agents suppress the malignant transformation and tumor progression by interfering with TNF-α-related functions in malignancies including RCC (22,31,32). A clinical trial demonstrated that intravenously injecting infliximab, an anti-TNF-α monoclonal antibody, decreases tumor size and prognosis in RCC patients, suggesting that TNF-α is a putative therapeutic target in such patients (33).…”

“…A preliminary study based on a randomized double-blind clinical trial and immunity are important for carcinogenesis and malignant invasiveness in multiple cancers (13,14). Moreover, various pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, tumor necrosis factor (TGF)-β, and interleukin (IL)-6 correlate with malignant transformation and occurrence of adverse events caused by anti-cancer therapies in various types of malignancies (15)(16)(17)(18)(19)(20)(21)(22). Previous reports have shown that RJ regulates the synthesis of these pro-inflammatory cytokines (23)(24)(25).…”

Association of Tumor Size with Risk of Lymph Node Metastasis in Clear Cell Renal Cell Carcinoma: A Population-Based Study

“…Kates et al found that male patients were 1.51 times more likely to develop LNM than females [ 17 ]. This may be attributed to suppression of RCC growth via estrogen/estrogen receptor signaling pathway [ 25 ]. Additionally, we found that higher T stage was closely associated with higher risk of LNM.…”

Sex-specific hormone changes during immunotherapy and its influence on survival in metastatic renal cell carcinoma

“…A population-based study recently reported that female sex was a significant predictor of poor renal cancer-specific mortality for advanced disease, however, only in postmenopausal period [ 50 ]. In addition, E2 has also been shown to inhibit RCC growth in vitro via an estrogen receptor-ß (ER-ß) dependent pathway [ 51 ]. Finally, hormonal agents such as medroxyprogesterone were initially shown to be active in metastatic RCC, although the response rates reported in various studies were modest, ranging from 7 to 25% [ 52 , 53 ].…”