SWAP-70 contributes to spontaneous transformation of mouse embryo fibroblasts.
SWAP-70 contributes to spontaneous transformation of mouse embryo fibroblasts.
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DOI：
10.1016/j.yexcr.2015.06.011
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发表时间：
2016-07
影响因子：
3.7
通讯作者：
Yu-Tzu Chang;C. Shu;Jing-Yang Lai;Ching-Yu Lin;Chih-Pin Chuu;K. Morishita;T. Ichikawa;R. Jessberger;Y. Fukui
中科院分区：
文献类型：
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作者：
Yu-Tzu Chang;C. Shu;Jing-Yang Lai;Ching-Yu Lin;Chih-Pin Chuu;K. Morishita;T. Ichikawa;R. Jessberger;Y. Fukui
小鼠胚胎成纤维细胞（MEFs）在动物培养后生长缓慢，但经过较长时间的培养后，其生长速度加快。我们发现缺乏SWAP-70的mef不能提高生长速率。它们保持正常的生长速度和增殖周期至少5年。通过表达人类SWAP-70来补充MEF克隆MEF1F2中SWAP-70的缺陷，在进一步长时间培养后，细胞快速生长。由此产生的细胞表现出一种转化表型，因为它们生长在彼此的顶部，不表现出接触抑制。当加入一种假定的SWAP-70抑制剂血根碱时，这种表型被逆转。对两个表达SWAP-70的克隆进行了详细的检测。即使在细胞密度变得非常高后，它们的cdc2和NFκB仍然被激活，这表明它们没有停止生长。其中一个克隆在软琼脂中形成菌落，并在裸鼠体内形成肿瘤。最近，又有一个克隆被转化为能够在软琼脂中形成菌落。我们维持了4个表达MEF1F2的人SWAP-70细胞系。4个无性系中有3个呈现转化表型。小鼠SWAP-70基因也促进mef的转化。综上所述，我们的数据表明SWAP-70不是一个典型的致癌基因，但它是mef自发转化所必需的。
Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, a putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs.