Sun Shiren, Du Rui, Gao Juan, Ning Xiaoxuan, Xie Huahong, Lin Xia, Liu Jie, Fan Daiming
State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
Pathology. 2009;41(4):335-41. doi: 10.1080/00313020902885003.
The pathological roles of Notch receptors in renal cell carcinoma (RCC) are still unclear, although Notch receptors have been shown to have an effect on many malignant tumours. Therefore, in this study, we examined the patterns of expression and clinical significance of Notch receptors in RCC.
Eighty-four cases of renal cell carcinoma tissues were detected by immunohistochemistry. Eleven paired fresh surgical renal cell carcinoma and adjacent non-neoplastic renal samples were analysed by Western blot and reverse transcriptase polymerase chain reaction. In addition, the expression of Notch receptors in renal cancer cell lines (A498 and 786-O) and human normal kidney tubule epithelial cell lines (HK-2 and HKC) were analysed by Western blot.
The expression levels of Notch1 and Notch4 were absent or significantly decreased in renal cell carcinoma tissues compared with the adjacent non-neoplastic tissues [Notch1: 22.6% (19/84) versus 78.7% (59/75); Notch4: 27.4% (23/84) versus 73.3% (55/75); p < 0.05). Moreover, the levels of expression of Notch1 and Notch4 were also markedly down-regulated in human renal cancer cell lines. Notch1 was negatively correlated with tumour stage, while Notch4 expression had no significant association with pathological parameters. The levels of expression of Notch2 and Notch3 were minimally detected in tumours and non-neoplastic tissues.
Our findings indicated that the expression of Notch receptors was deregulated and Notch signalling might play an important role in the progress of renal cell carcinoma.
尽管已表明Notch受体对许多恶性肿瘤有影响，但Notch受体在肾细胞癌（RCC）中的病理作用仍不清楚。因此，在本研究中，我们检测了RCC中Notch受体的表达模式及其临床意义。
采用免疫组织化学法检测84例肾细胞癌组织。通过蛋白质印迹法和逆转录聚合酶链反应分析11对新鲜手术切除的肾细胞癌及相邻的非肿瘤性肾组织样本。此外，采用蛋白质印迹法分析肾癌细胞系（A498和786 - O）和人正常肾小管上皮细胞系（HK - 2和HKC）中Notch受体的表达。
与相邻的非肿瘤组织相比，肾细胞癌组织中Notch1和Notch4的表达水平缺失或显著降低[Notch1：22.6%（19/84）对78.7%（59/75）；Notch4：27.4%（23/84）对73.3%（55/75）；p < 0.05]。此外，人肾癌细胞系中Notch1和Notch4的表达水平也明显下调。Notch1与肿瘤分期呈负相关，而Notch4的表达与病理参数无显著关联。在肿瘤组织和非肿瘤组织中，Notch2和Notch3的表达水平最低。
我们的研究结果表明，Notch受体的表达失调，Notch信号通路可能在肾细胞癌的进展中起重要作用。
