High-level expression of Notch1 increased the risk of metastasis in T1 stage clear cell renal cell carcinoma.
High-level expression of Notch1 increased the risk of metastasis in T1 stage clear cell renal cell carcinoma.
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Notch1的高水平表达增加了T1期透明细胞肾细胞癌的转移风险
DOI：
10.1371/journal.pone.0035022
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Ai Q;Ma X;Huang Q;Liu S;Shi T;Zhang C;Zhu M;Zhang Y;Wang B;Ni D;Li H;Zheng T;Zhang X
背景肾透明细胞癌（clear cell renal cell carcinoma，ccRCC）的转移基本上发生在晚期肿瘤，但T1期也有转移，且无明确的分子原因，导致手术方式选择不当，预后差。Notch信号转导是一种保守的、广泛表达的信号通路，其介导正常发育和肿瘤发生中的各种细胞过程。本研究旨在探讨Notch信号在T1期ccRCC转移中的作用及其机制。方法/主要发现Notch1和Jagged1的表达在从51名ccRCC患者获得的肿瘤组织和匹配的正常邻近组织中进行了分析。与非肿瘤组织相比，Notch1和Jagged1在肿瘤中的表达在mRNA和蛋白水平上均显著升高。根据肿瘤分期将局限性和转移性肿瘤的组织样本分为三组，并分析Notch1和Jagged1的相对mRNA表达。与局限性肿瘤相比，Notch 1在T1期转移性肿瘤中的表达显著升高，而Jagged 1在各期局限性肿瘤和转移性肿瘤中的表达无统计学差异。T1期ccRCC中转移瘤的平均大小明显大于局限性肿瘤，Notch 1的表达与肿瘤直径呈显著正相关。通过用Notch 1和Jagged 1的全长表达质粒转染786-O、Caki-1和HKC细胞系来研究Notch信号传导的功能意义。与相应的对照组相比，所有细胞系均表现出细胞增殖和迁移的显著促进，而细胞周期不受影响。结论/意义Notch信号通路高表达通过刺激肿瘤细胞增殖和迁移增加T1期ccRCC转移的风险，这可能有助于ccRCC手术方式的选择和预后判断。
Background Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. Methodology/Principal Findings The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1. Compared to the corresponding controls, all cell lines demonstrated significant promotion in cell proliferation and migration while cell cycle remained unaffected. Conclusions/Significance High-level expression of Notch signaling increased the risk of metastasis in T1 stage ccRCC by stimulating the proliferation and migration of tumor cells, which may be helpful for the selection of suitable operation method and prognosis of ccRCC.
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DOI：
10.1016/s0022-2143(97)90180-3
发表时间：
1997-03-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Racusen, LC;Monteil, C;Morin, JP
通讯作者：
Morin, JP
影响因子：
--
作者：
Jung M;Ramankulov A;Roigas J;Johannsen M;Ringsdorf M;Kristiansen G;Jung K
通讯作者：
Jung K
影响因子：
50.3
作者：
Sonoshita, Masahiro;Aoki, Masahiro;Taketo, Makoto Mark
通讯作者：
Taketo, Makoto Mark
影响因子：
11.2
作者：
Yeh, Tien-Shun;Wu, Chew-Wun;Chi, Chin-Wen
通讯作者：
Chi, Chin-Wen
影响因子：
10.3
作者：
FOGH, J;WRIGHT, WC;LOVELESS, JD
通讯作者：
LOVELESS, JD