Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma.
Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma.
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DOI：
10.1111/cas.12649
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发表时间：
2015-05
期刊：
影响因子：
5.7
通讯作者：
Ooi A
中科院分区：
文献类型：
--
作者：
Nakamura R;Oyama T;Tajiri R;Mizokami A;Namiki M;Nakamoto M;Ooi A
神经表皮生长因子样（NELL）1和2构成了一个多聚体和多模块胞外糖蛋白家族。虽然已经报道了NELL1的成骨作用和NELL2在神经发育中的功能，但它们在癌症中的表达和功能在很大程度上是未知的。在这项研究中，我们研究了NELL1和NELL2的表达在肾细胞癌（RCC）的临床标本和细胞系。我们发现，尽管NELL1和NELL2蛋白在RCC标本的非癌区域的肾小管中强烈表达，但它们的表达在癌区域中显著下调。在RCC细胞系中也检测到NELL1和NELL2 mRNA表达的沉默。NELL1/2启动子甲基化状态分析表明，在RCC细胞系中NELL1和NELL2基因的CpG岛是高甲基化的。NELL1和NELL2与RCC细胞结合，表明这些细胞表达NELL1和NELL2的受体，该受体可以抑制信号。此外，我们发现NELL1和NELL2都抑制RCC细胞迁移，并且NELL1进一步抑制RCC细胞粘附。这些结果表明，NELL基因表达的沉默启动子高甲基化发挥作用，在肾细胞癌的进展，影响癌细胞的行为。
Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior.
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DOI：
10.1016/s0169-328x(99)00342-3
发表时间：
2000-03-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Oyasu, M;Kuroda, S;Saito, N
通讯作者：
Saito, N
影响因子：
4.8
作者：
Matsuoka, H;Obama, H;Nakamoto, M
通讯作者：
Nakamoto, M
影响因子：
3.5
作者：
Jiang, Yulan;Obama, Hiroya;Kuan, Soh Leh;Nakamura, Ritsuko;Nakamoto, Chizu;Ouyang, Zhufeng;Nakamoto, Masaru
通讯作者：
Nakamoto, Masaru
DOI：
10.1073/pnas.91.21.9700
发表时间：
1994-10-11
影响因子：
11.1
作者：
HERMAN, JG;LATIF, F;BAYLIN, SB
通讯作者：
BAYLIN, SB
影响因子：
1.9
作者：
Maeda, K;Matsuhashi, S;Kuroda, S
通讯作者：
Kuroda, S