No Mutations of Lysophosphatidic Acid Receptor Genes in Lung Adenocarcinomas Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats

Wakabayashi, Naoko; Tsujino, Megumu; Tajiri, Masaki; Taki, Midori; Koshino, Ayumi; Ikeda, Hiroko; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

doi:10.1293/tox.23.63

Cited by 11 publications

(5 citation statements)

References 22 publications

(25 reference statements)

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“…These results suggest that mutations of the Lpar1 gene may be involved in the acquisition of growth advantage from adenomas to adenocarcinomas during rat lung carcinogenesis induced by BHP 20 . By contrast, no mutation of the Lpar2 , Lpar3 , Lpar4 and Lpar5 genes was detected in this model 21 .…”

Section: Genetic Alterationscontrasting

confidence: 61%

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: Genetic Alterationscontrasting

confidence: 61%

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

2011

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“…These findings demonstrated that Lpa1 mutations may be involved during rat lung and liver carcinogenesis. By contrast, no mutations of Lpa2, Lpa3, Lpa4, or Lpa5 genes were detected in lung adenocarcinomas induced by BHP [33]. In the present study, we also performed PCR‐SSCP analysis to evaluate whether Lpa5 gene mutations exist in rat tumor cell lines and HCCs, but detected no mutations.…”

Section: Discussionmentioning

confidence: 67%

Possible involvement of lysophosphatidic acid receptor‐5 gene in the acquisition of growth advantage of rat tumor cells

Okabe¹,

Hayashi²,

Yamawaki³

et al. 2011

Molecular Carcinogenesis

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Aberrant expressions of lysophosphatidic acid (LPA) receptor genes have been reported in tumor cells. Here, we measured the expression levels of the Lpa5 gene and its DNA methylation status in rat tumor cells, and investigated cell growth effects of LPA in Lpa5 expressed cells. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis revealed that increased expressions of the Lpa5 gene were detected in rat liver-derived hepatoma RH7777 and lung-derived adenocarcinoma RLCNR cells. For the analysis of methylation status, bisulfite sequencing was performed with RH7777 and RLCNR cells and compared with other tumor cells and liver epithelial cells. The Lpa5 gene in Lpa5 unexpressed cells and liver epithelial cells were highly methylated in the 5' upstream region. In contrast, the Lpa5 gene in RH7777 and RLCNR cells was unmethylated, correlating with increased expressions of Lpa5. In the assays for cell growth effects of LPA, LPA enhanced cell proliferation and motility in RH7777 and RLCNR cells. LPA also stimulated cell invasion in RLCNR, but not in RH7777 cells. In rat liver and lung tumors induced by nitroso-compounds, 4 out of 6 hepatocellular carcinomas and 5 out of 6 lung adenocarcinomas indicated increased expressions of Lpa5 with unmethylated status. These results suggest that increased Lpa5 expressions due to aberrant DNA methylation may be involved in the acquisition of growth advantage of rat tumor cells.

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“…Moreover, LPA1 gene mutations were also detected in not only lung adenocarcinomas but also preneoplastic lesions in rats [16]. In contrast, no mutations of the LPA2, LPA3, LPA4, and LPA5 genes were found in rat lung adenocarcinomas [22]. These findings suggest that the LPA1 gene mutations may play an important role in the development of rat tumor cells as well as aberrant LPA receptor gene expressions but not LPA2, LPA3, LPA4, and LPA5 mutations.…”

Section: Discussionmentioning

confidence: 82%

Differential expressions and DNA methylation patterns of lysophosphatidic acid receptor genes in human colon cancer cells

et al. 2010

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Lysophosphatidic acid (LPA), which is a bioactive phospholipid, interacts with specific G protein-coupled transmembrane receptors. Recently, alterations of LPA receptor genes have been reported in some tumor cells. In this study, we examined the expression profiles and DNA methylation status of LPA receptor 1-5 (LPA1-5) genes in human colon cancer cells and also looked for the mutations. Reverse transcription-polymerase chain reaction (PCR) and bisulfite sequencing analyses were carried out. While LPA1, LPA2, and LPA4 genes were expressed in DLD1, SW480, HCT116, CaCo-2, SW48, and LoVo cells, the expressions of LPA3 and LPA5 genes were various. These expression levels were correlated with DNA methylation status in the 5' upstream regions of the LPA receptor genes. Mutation analysis was also performed using a PCR-single-strand conformation polymorphism method. Although no mutations in LPA1, LPA3 and LPA5 genes were found in all types of cells, LPA2 mutations in DLD1 and SW48 cells, and LPA4 mutation were found in DLD1 cells. On the basis of the present results, we demonstrate that these colon cancer cells will be available to understanding the molecular pathway through LPA receptors in the development of tumor cells, and that LPA receptors may be new molecular targets for therapeutic approaches and chemoprevention.

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No Mutations of Lysophosphatidic Acid Receptor Genes in Lung Adenocarcinomas Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats

Cited by 11 publications

References 22 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

Possible involvement of lysophosphatidic acid receptor‐5 gene in the acquisition of growth advantage of rat tumor cells

Differential expressions and DNA methylation patterns of lysophosphatidic acid receptor genes in human colon cancer cells

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