Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Okabe, Kyoko; Hayashi, Mikihiro; Wakabayashi, Naoko; Yamawaki, Yasuna; Teranishi, Miki; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

doi:10.1159/000321898

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…In mouse tumor cells, aberrant DNA methylation of the Lpar1 gene was detected in B16F0 melanoma cells, FM3A mammary carcinoma cells and L1210 leukemia cells. The Lpar3 gene in LL/2 lung tumor cells, B16F0, FM3A and L1210 cells was also hypermethylated compared with their adjacent normal tissues 43 .…”

Section: Epigenetic Alterationsmentioning

confidence: 93%

Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models

2011

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Lysophosphatidic acid (LPA) is a bioactive mediator and induces several biological effects, including cell proliferation, migration, morphogenesis and differentiation. LPA interacts with at least six G protein-coupled receptors (GPCRs), including LPA receptor-1 (LPA1), LPA2, LPA3, LPA4, LPA5 and LPA6. These receptors show different biological functions through the binding of LPA, depending on the type of cells. In human malignancies, a high level of LPA production was found in plasma and ascites in ovarian cancer cases. Moreover, aberrant expression levels of LPA receptor genes were detected in some cancer cells. Therefore, it is suggested that LPA receptors may be involved in the pathogenesis of tumor cells as well as LPA per se. Recently, we have reported that alterations of LPA receptor genes also occur in rodent tumors. In this review, we summarize the recent evidence in the investigations of LPA receptor alterations in rodent tumors by experimental models.

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Section: Epigenetic Alterationsmentioning

confidence: 93%

Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models

2011

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“…Furthermore, the expression levels of multidrug resistance 1a (Mdr1a) , Mdr1b and glutathione S-transferase mu1 (Gstm1) genes were also measured. FM3A cells expressed Lpar2 , but not Lpar1 and Lpar3 due to DNA methylation 12 .…”

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confidence: 89%

“…Since the Lpar3 gene expression in FM3A cells was undetectable 12 , we generated Lpar3 -expressing FM3A-a3A9 cells (Fig. 1A).…”

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confidence: 99%

Enhancement of Drug Resistance by Lysophosphatidic Acid Receptor-3 in Mouse Mammary Tumor FM3A Cells

et al. 2012

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Lysophosphatidic acid (LPA) acts as a simple phospholipid that interacts with G protein-coupled transmembrane LPA receptors. Recently, it has been reported that each LPA receptor plays different biological roles in acquisition of the malignant property of tumor cells. In this study, to assess the involvement of LPA receptor-3 (LPA3) in cell survival after treatment with anticancer drugs, we generated Lpar3-expressing FM3A-a3A9 cells from mouse mammary tumor FM3A cells and examined the cell survival rate after treatment with anticancer drugs compared with Lpar3-unexpressing cells. Cells were treated with 0.005 to 10 μM of cisplatin (CDDP) or doxorubicin (DOX) for 3 days. For the CDDP and DOX treatments, the cell survival rate of FM3A-a3A9 cells was significantly higher than that of Lpar3-unexpressing cells. The expression level of the Mdr1a gene in FM3A-a3A9 cells was higher than that of Lpar3-unexpressing cells, whereas no significant difference in multidrug resistance 1b (Mdr1b) and glutathione S-transferase mu1 (Gstm1) expressions was found. These results suggest that LPA3 may enhance the cell survival rate after treatment with anticancer drugs in mouse mammary tumor cells, correlating with increased expression of the Mdr1 gene.

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“…Mutations of the Lpar1 gene are frequently observed in rat liver and lung tumors . In addition, aberrant expression of LPA receptor genes due to DNA methylation was found in human and mouse tumor cells . LPA is present in mammalian serum at concentrations of 1 to 5 μM and is rapidly released from activated platelets .…”

Section: Introductionmentioning

confidence: 99%

Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB‐F344 cells

Hirane

Ishii

Tomimatsu

et al. 2015

Molecular Carcinogenesis

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Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA to LPA ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc.

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Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Cited by 13 publications

References 34 publications

Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models

Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models

Enhancement of Drug Resistance by Lysophosphatidic Acid Receptor-3 in Mouse Mammary Tumor FM3A Cells

Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB‐F344 cells

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