Inhibited Notch1Expression And Notch Signaling In Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a common disease and one of the lethal ones in theurogenital system. Patients with early stage RCC can be cured or well treated by surgicalprocedures, while patients who have developed late stage RCC can not get goodprognosis. In recent years，the use of IL-2，IFN-α and several kinds of targeted drugs hasmade some progress in the treatment of late stage RCC. It is still an urgency to try tofigure out the mechanisms of RCC and develop novel drugs.A lot of researchers have proved that Notch signaling is related to various kinds oftumors and whether it functions as an oncogene or a tumor suppressor is determined bycell types and tumor microenvironment. Up to now, many studies have been performed tostudy this signaling in RCC. But, researchers are far away from agreeing with each otheron the exact role of Notch signaling in RCC.In order to explore the expression of Notch1and Notch signaling in RCC and to evaluate its correlation with clinicopathological characters in RCC, we appliedimmunohistochemistry (IHC) and Western-blot to detect the Notch1expression in RCCtumor tissues and adjacent normal tissues from56RCC patients. In addition,we alsodetected the mRNA level of Notch1and its target gene Hes1in both RCC tissue samplesand RCC and normal renal epithelial cell lines.Our IHC results showed that the RCC tumor tissues had much lower Notch1expression when compared with the matched adjacent normal tissues. The mRNA level ofboth Notch1and Hes1was also lower in RCC tumor tissues than in normal renal tissues.Statistical analysis indicated that the early stage (AJCC I+II) RCC had higher levels ofNotch1expression than the late stage (AJCC III+IV) and Notch1expression was reverselycorrelated with Fuhrman grade. Besides, lower mRNA of Notch1and Hes1was alsodetected in RCC cell line786-O than that in renal epithelial cell line HK-2, suggesting anattenuated Notch signaling in RCC cell lines.Our results showed that Notch1and Notch signaling may have tumor suppressivefunction in RCC and decreased Notch1expression was associated with progressive tumorstage, indicating Notch1and Notch signaling might be used as biological marker for theprediction of RCC prognosis.