Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers
Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers
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DOI：
10.1016/j.canlet.2008.03.015
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发表时间：
2008-08-18
期刊：
影响因子：
9.7
通讯作者：
Andrulis, Irene L.
中科院分区：
文献类型：
--
作者：
Huggins, Christopher Jack;Andrulis, Irene L.
LIMD1是相关蛋白的ZYXIN家族成员，该家族包括AJUBA、TRIP6、LPP、WTIP、migfilin和ZYXIN。LIMD1基因座位于3p21.3，已表明在肿瘤组织中会发生杂合性缺失，这提示其可能具有肿瘤抑制功能。为了进一步了解LIMD1在癌症中的作用，我们对LIMD1蛋白的内源性表达进行了特征分析，并评估了LIMD1 RNA在原发性人类乳腺肿瘤中的表达。发现LIMD1水平在整个细胞周期中保持恒定，但在HeLa细胞有丝分裂期间LIMD1会被磷酸化。此外，我们观察到内源性LIMD1与纽蛋白在粘着斑处共定位。在缺乏LIMD1表达的MDA - MB435细胞系中，我们检测到假定启动子区域的甲基化。发现LIMD1 mRNA表达在原发性人类乳腺肿瘤中存在差异；然而，人类乳腺癌中LIMD1表达的差异与预测的启动子区域的DNA甲基化无关。这些结果表明，一些乳腺肿瘤的LIMD1 RNA表达发生了改变，并且LIMD1可能通过粘着斑参与细胞锚定以及细胞周期，特别是在有丝分裂期间。（C）2008爱思唯尔爱尔兰有限公司。保留所有权利。
LIMD1 is a member of the ZYXIN family of related proteins which includes AJUBA, TRIP6, LPP, WTIP, migfilin, and ZYXIN. The LIMD1 locus, 3p21.3, has been shown to undergo loss of heterozygosity in neoplastic tissues, suggesting potential tumor suppressor function. To further understand the role of L1MD1 in cancer, we have characterized endogenous expression of the LIMD1 protein and evaluated LIMD1 RNA expression in primary human breast tumors. LIMD1 levels were found to be constant throughout the cell cycle, but LIMD1 is phosphorylated during mitosis in HeLa cells. In addition, we observed colocalization of endogenous LIMD1 with vinculin at focal adhesions. In the MDA-MB435 cell line, which lacks LIMD1 expression, we detected methylation of the Putative promoter region. LIMD1 mRNA expression was found to vary among primary human breast tumors; however, differences in LIMD1 expression in human breast cancers were not associated with DNA methylation of the predicted promoter region. These results suggest that some breast tumors have altered expression of LIMD1 RNA and that LIMDI may be involved in cell anchoring via focal adhesions and in the cell cycle, particularly during mitosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.