Frequent mutations of lysophosphatidic acid receptor-1 gene in rat liver tumors
Frequent mutations of lysophosphatidic acid receptor-1 gene in rat liver tumors
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DOI：
10.1016/j.mrfmmm.2008.10.005
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发表时间：
2009-01-15
影响因子：
2.3
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Obo, Yumi;Yamada, Takanori;Tsujiuchi, Toshifumi
溶血磷脂酸(LPA)是一种生物活性磷脂，能刺激细胞增殖、迁移，并保护细胞免受凋亡。它与特定的G蛋白偶联跨膜受体相互作用，包括LPA1到LPA5。在本研究中，为了阐明LPA I基因突变在肝细胞癌发生发展中的作用，我们研究了外源性和内源性肝细胞癌模型诱导的大鼠肝细胞癌中LPA1突变。我们用N-亚硝基二乙胺(DEN)和胆碱缺乏的L氨基酸限定饲料(CDAA)诱导大鼠肝细胞癌。从DEN诱导的15个肝细胞和CDAA饮食诱导的12个肝细胞中提取RNA。采用逆转录-聚合酶链式反应-单链构象多态(SSCP)分析和核苷酸测序的方法检测LPA1基因突变。DEN诱发的15例肝癌中有7例(46.7%)检测到错义突变。CDAA饮食诱导的12例肝癌中也有5例(41.7%)出现错义突变。这些结果表明，在DEN和CDAA饮食诱导的大鼠肝癌细胞中，LPA1基因发生了突变，提示LPA1突变可能主要参与了大鼠肝癌的发生。(C)2008爱思唯尔B.V.保留所有权利。
Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with Specific G protein-coupled transmembrane receptors, including LPA1 to LPA5. In the present study, to clarify an involvement of LPA I gene alterations in the development of hepatocellular carcinomas (HCCs) we investigated the LPA1 mutations in rat HCCs induced by exogenous and endogenous liver carcinogenesis models. We induced HCCs in rats with N-nitrosodiethylamine (DEN) and a choline-deficient L-amino acid-defined (CDAA) diet. RNAs were extracted from 15 HCCS induced by DEN and 12 HCCs induced by the CDAA diet. To identify LPA1 mutations, reverse transcription (RT) - polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing, was performed. Missense mutations were detected in 7 out of 15 HCCs (46.7%,) induced by DEN. Five Out of 12 HCCs (41.7%,) induced by the CDAA diet also showed missense mutations. These results demonstrated that mutations in LPA1 gene occur in rat HCCs induced by DEN and the CDAA diet, suggesting that LPA1 mutations may be essentially involved ill rat liver carcinogenesis. (c) 2008 Elsevier B.V. All rights reserved.