Renz Malte, Betz Beate, Niederacher Dieter, Bender Hans Georg, Langowski Jörg
Division of Biophysics of Macromolecules, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, TP3, D-69120 Heidelberg, Germany.
Int J Cancer. 2008 Apr 1;122(7):1476-82. doi: 10.1002/ijc.23215.
The CapG protein, a Gelsolin-related actin-binding protein, is expressed at higher levels in breast cancer, especially in metastasizing breast cancer, than in normal breast epithelium. Furthermore, it is known that an increased expression of the CapG protein triggers an increase in cell motility. According to in vitro experiments, it was supposed that it is the nuclear fraction of the protein, which causes the increase in cell motility. Here, we examined the dynamical distribution of the CapG protein within the living cell, i.e. the import of the CapG protein into the nucleus. The nuclear import kinetics of invasive, metastasizing breast cancer cells were compared to the import kinetics of non-neoplastic cells similar to normal breast epithelium. FRAP kinetics showed a highly significant increase in the recovery of photobleached CapG-eGFP in the cancer cells, so that a differentiation of invasive, metastasizing cells and non-invasive, non-metastasizing cells on the basis of transport processes of the CapG protein between the nucleus and the cytoplasm seems to be possible. Comprehension of the mobility and compartmentalization of the CapG protein in normal and in cancer cells in vivo could constitute a new basis to characterize the invasiveness and metastasizing potential of breast cancer.
CapG蛋白是一种与凝溶胶蛋白相关的肌动蛋白结合蛋白，在乳腺癌中，尤其是在转移性乳腺癌中的表达水平高于正常乳腺上皮。此外，已知CapG蛋白表达增加会引发细胞运动性增强。根据体外实验推测，是该蛋白的核部分导致了细胞运动性增加。在此，我们研究了CapG蛋白在活细胞内的动态分布，即CapG蛋白向细胞核的导入。将侵袭性转移性乳腺癌细胞的核输入动力学与类似于正常乳腺上皮的非肿瘤细胞的输入动力学进行了比较。荧光恢复动力学显示，癌细胞中光漂白的CapG-eGFP的恢复有显著增加，因此基于CapG蛋白在细胞核与细胞质之间的转运过程，区分侵袭性转移性细胞和非侵袭性非转移性细胞似乎是可行的。了解CapG蛋白在体内正常细胞和癌细胞中的流动性和区室化可能构成表征乳腺癌侵袭性和转移潜能的新基础。
