Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2.
Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2.
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DOI：
10.3892/ijo.19.5.963
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发表时间：
2001-11
影响因子：
5.2
通讯作者：
Masaru Katoh
中科院分区：
文献类型：
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作者：
Masaru Katoh
小鼠Nkd是一种Dishevelled结合蛋白，在WNT -β-catenin- TCF信号通路中起负调节作用。在这里，人NKD 1和NKD 2被克隆和表征。NKD 1和NKD 2分别编码470和451个氨基酸的多肽。NKD 1和NKD 2在NH 1、NH 2、NH3和NH 4结构域中具有更高的同源性，显示出43.8%的总氨基酸同一性。NKD 1和NKD 2的NH 2结构域含有EF-手状基序。NKD 1和NKD 2基因的外显子-内含子结构由10个外显子组成，具有很好的保守性。NKD 1在胎儿肾脏中高度表达，而NKD 2在胎儿肾脏、肺和成人肺中中度表达。NKD 1在结肠直肠癌细胞系SW 480、胃癌细胞系TMK 1和胰腺癌细胞系Hs 700 T中上调。NKD 2在胃癌细胞系MKN 45、胰腺癌细胞系BxPC-3和食管癌细胞系TE 6和TE 13中上调。10例胃癌中1例NKD 1和NKD 2同时表达上调，2例NKD 1和NKD 2同时表达下调。NKD 1或NKD 2的上调可能是由于负反馈机制。或者，NKD 1或NKD 2的遗传改变可能导致WNT -β-连环蛋白- TCF信号通路的激活。
Mouse Nkd is a Dishevelled-binding protein, functioning as a negative regulator of WNT - beta-catenin - TCF signaling pathway. Here, human NKD1 and NKD2 were cloned and characterized. NKD1 and NKD2 were predicted to encode 470- and 451-amino-acid polypeptide, respectively. NKD1 and NKD2, showing 43.8% total amino-acid identity, were more homologous in the NH1, NH2, NH3, and NH4 domains. The NH2 domain of NKD1 and NKD2 contained the EF-hand motif. Exon-intron structures of NKD1 and NKD2 genes, consisting of 10 exons, were well conserved. NKD1 was highly expressed in fetal kidney, while NKD2 was moderately expressed in fetal kidney, lung, and adult lung. NKD1 was up-regulated in colorectal cancer cell line SW480, gastric cancer cell line TMK1, and pancreatic cancer cell line Hs700T. NKD2 was up-regulated in gastric cancer cell line MKN45, pancreatic cancer cell line BxPC-3, and esophageal cancer cell lines TE6, and TE13. NKD1 and NKD2 were up-regulated together in 1 case of primary gastric cancer out of 10 cases, and were down-regulated together in 2 cases. Up-regulation of NKD1 or NKD2 might be due to a negative feed-back mechanism. Alternatively, genetic alteration of NKD1 or NKD2 might lead to activation of the WNT - beta-catenin - TCF signaling pathway.