Transfection of keratin 18 gene in human breast cancer cells causes induction of adhesion proteins and dramatic regression of malignancy in vitro and in vivo
Transfection of keratin 18 gene in human breast cancer cells causes induction of adhesion proteins and dramatic regression of malignancy in vitro and in vivo
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DOI：
10.1158/1541-7786.mcr-04-0117
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发表时间：
2005-07-01
影响因子：
5.2
通讯作者：
Schaller, G
中科院分区：
文献类型：
--
作者：
Bühler, H;Schaller, G
这项研究表明，肿瘤细胞中角蛋白18(K18)的高表达与体外侵袭力的降低和裸鼠体内缺乏致瘤性有关。我们以前发现K18的高表达与良好的预后相关，而降低K18的表达增加了已建立的乳腺癌细胞系的侵袭性。为了证实这些观察结果，我们将人K18基因导入人乳腺癌细胞系MDA-MB-231，并分离到一个稳定的高表达克隆。K18的强制表达与亲本细胞株中先前强烈的波形蛋白表达完全丧失、K18二聚化伙伴K8的诱导以及黏附蛋白的上调有关。伴随着这些变化的是，K18转基因细胞在体外和体内的侵袭性显著降低。我们的结论是，强制重新表达K18至少会导致肿瘤细胞的部分再分化，随后相应地会导致恶性表型的退化。
This study shows that high keratin 18 (K18) expression in tumor cells is associated with reduced invasiveness in vitro and lack of tumorigenicity in nude mice. We previously showed that high K18 expression correlated with a good prognosis and that reducing K18 expression increased the aggressiveness of established breast cancer cell lines. To confirm these observations, we transfected the human K18 gene into the human breast cancer cell line MDA-MB-231 and isolated a stable overexpressing clone. The forced K18 expression was associated with a complete loss of the previously strong vimentin expression in the parent cell line, induction of the K18 dimerization partner K8, and up-regulation of adhesion proteins. These changes were accompanied by a dramatic reduction in the aggressiveness of the K18 transfectants in vitro and in vivo. We conclude that forced reexpression of K18 causes at least partial redifferentiation of the tumor cell, followed by a corresponding regression of malignant phenotype.