Loss of lysophosphatidic acid receptor-3 enhances cell migration in rat lung tumor cells
Loss of lysophosphatidic acid receptor-3 enhances cell migration in rat lung tumor cells
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DOI：
10.1016/j.bbrc.2011.01.051
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发表时间：
2011-02-18
影响因子：
3.1
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Hayashi, Mai;Okabe, Kyoko;Tsujiuchi, Toshifumi
溶血磷脂酸（LPA）具有多种生物学效应，如细胞增殖、分化和迁移。LPA与G蛋白偶联的跨膜LPA受体相互作用。在我们之前的报告中，我们检测到LPA受体-1（Lpar 1）表达的缺失是由于其在大鼠肿瘤细胞系中的异常DNA甲基化。在这项研究中，以评估参与的其他LPA受体，Lpar 3，在大鼠肺肿瘤细胞的发病机制，我们测量了Lpar 3基因的表达水平和其DNA甲基化状态的逆转录（RT）-聚合酶链反应（PCR）和亚硫酸氢盐测序分析，分别。与正常肺组织相比，RLCNR肺腺癌细胞显示Lpar 3的表达降低。在Lpar 3的5'上游区域，正常肺组织未甲基化。相比之下，RLCNR细胞高度甲基化，与Lpar 3表达减少相关。基于这些结果，我们产生了表达Lpar 3的RLCNR-a3细胞，并测量了细胞迁移能力。有趣的是，RLCNR-a3细胞的细胞迁移显著低于RLCNR细胞。这项研究表明，由于异常DNA甲基化导致的Lpar 3缺失可能参与大鼠肺肿瘤细胞的进展。(C)2011 Elsevier Inc. All rights reserved.
Lysophosphatidic acid (LPA) indicates several biological effects, such as cell proliferation, differentiation and migration. LPA interacts with G protein-coupled transmembrane LPA receptors. In our previous report, we detected that loss of the LPA receptor-1 (Lpar1) expression is due to its aberrant DNA methylation in rat tumor cell lines. In this study, to assess an involvement of the other LPA receptor, Lpar3, in the pathogenesis of rat lung tumor cells, we measured the expression levels of the Lpar3 gene and its DNA methylation status by reverse transcription (RT)-polymerase chain reaction (PCR) and bisulfite sequencing analyses, respectively. RLCNR lung adenocarcinoma cells showed reduced expression of the Lpar3, compared with normal lung tissues. In the 5' upstream region of the Lpar3, normal lung tissues were unmethylated. By contrast, RLCNR cells were highly methylated, correlating with reduced expressions of the Lpar3. Based on these results, we generated the Lpar3-expressing RLCNR-a3 cells and measured the cell migration ability. Interestingly, the cell migration of RLCNR-a3 cells was significantly lower than that of RLCNR cells. This study suggests that loss of the Lpar3 due to aberrant DNA methylation may be involved in the progression of rat lung tumor cells. (C) 2011 Elsevier Inc. All rights reserved.