Phosphorylated KDR can be located in the nucleus of neoplastic cells
Phosphorylated KDR can be located in the nucleus of neoplastic cells
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DOI：
10.1038/sj.cr.7310012
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发表时间：
2006-01-01
期刊：
影响因子：
44.1
通讯作者：
Pezzella, F
中科院分区：
文献类型：
--
作者：
Blazquez, C;Cook, N;Pezzella, F
KDR（激酶插入结构域受体）磷酸化诱导最终导致细胞增殖和存活的几种效应。KDR一旦被激活，与细胞核通讯的精确机制开始被理解，但还没有完全解开。文献中报道的两项动物细胞系的体外研究表明，在VEGF刺激后，KDR实际上在细胞核内易位。我们的目的是研究这种易位是否发生在人体细胞在体外和体内。利用激光扫描共聚焦显微镜，在细胞系和肿瘤样品中发现磷酸化和总KDR的可变核定位。在人类肿瘤细胞系中，低氧刺激大大增加了总KDR的核量，但磷酸化形式的核量较少。仅在缺氧和VEGF刺激后，在这些细胞的细胞核中观察到磷酸化和总KDR的表达急剧增加。我们的结论是，肿瘤细胞显示了可变的表达总的和磷酸化的KDR在细胞核中。核位置的确切功能含义仍有待确定。
KDR (kinase insert domain receptor) phosphorylation induces several effects which lead eventually to cell proliferation and survival. The precise mechanisms by which KDR, once it is activated, communicates with the nucleus are starting to be understood but have not yet been completely untavelled. Two in vitro studies on animal cell lines reported in the literature have demonstrated that, following stimulation with VEGF, KDR is actually translocated within the nucleus. Our aim was to investigate whether this translocation occurs in human cells both in vitro and in vivo. Using laser scanning confocal microscopy, a variable nuclear localization of phosphorylated and total KDR in cell lines and tumour samples was found. In human neoplastic cell lines, hypoxic Stimulation greatly increased the nuclear amount of total KDR but less so that of the phosphorylated form. Only after hypoxia and VEGF stimulation there was a comparably increased expression of phosphorylated and total KDR observed in the nuclei of these cells. We conclude that neoplastic cells show a variable expression of total and phosphorylated KDR in the nucleus. The precise functional meaning of nuclear location remains to be established.