Infrequent Mutation of Lysophosphatidic Acid Receptor-1 Gene in Hamster Pancreatic Duct Adenocarcinomas and Established Cell Lines

Journal of Toxicologic Pathology (Impact Factor: 0.53). 03/2009; 22(1):89-92. DOI: 10.1293/tox.22.89
Source: PubMed


To evaluate the involvement of lysophosphatidic acid receptor-1 (LPA1) gene alteration in pancreatic carcinogenesis, we investigated mutations in the LPA1 gene in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 30 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/10, 10%) in the form of a GGA to GTA (Gly to Val) transversion at codon 355, and no mutations were detected in the three cell lines. These results suggest that the LPA1 gene mutation may play roles in a limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.

Download full-text


Available from: Kanya Honoki
  • Source
    • "In conclusion, the present study detected no mutations of the LPA2, LPA3, LPA4 and LPA5 genes in rat lung adenocarcinomas induced by BHP. Recently, we reported LPA1 gene mutations in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters. 24 To better understand the involvement of LPA receptor genes during carcinogenesis, we are currently investigating LPA2, LPA3, LPA4 and LPA5 gene mutations in hamster pancreatic duct adenocarcinomas. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation and migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, frequent mutations of the LPA receptor-1 (LPA1) gene were detected in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). In this study, to evaluate the involvement of other LPA receptor gene alterations during lung carcinogenesis, we investigated mutations of the LPA2, LPA3, LPA4 and LPA5 genes in lung adenocarcinomas induced by BHP in rats. Fifteen male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in their drinking water for 12 weeks and then maintained without further treatment until sacrifice at 25 weeks, and 15 adenocarcinomas were obtained. Genomic DNAs were extracted from frozen tissues, and the LPA2, LPA3, LPA4 and LPA5 genes were examined for mutations, using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. No mutations of LPA2, LPA3, LPA4 and LPA5 were detected in the 15 adenocarcinomas. These results suggest that alterations due to LPA2, LPA3, LPA4 and LPA5 gene mutations might not be involved in the development of lung adenocarcinomas induced by BHP in rats.
    Full-text · Article · Mar 2010 · Journal of Toxicologic Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: In example of OSC, BrCN, O3 molecules, we show that the fitting method suggested in our previous work is applicable for retrieving interatomic separations of molecules with two structural parameters from high-order harmonics generated from these molecules in interaction with intense ultra-short infrared laser pulses. For linear molecules such as OSC, BrCN we find that the accurate structural information can be obtained using a small set of harmonics of only one alignment angle. However, for the planar molecule, O3, we need high harmonics of at least two alignment angles to retrieve two structural parameters of the molecule. We show that for both linear and planar molecules, the interatomic separations can also be retrieved from harmonics generated by isotropically oriented molecules. To develop the method, we also apply the genetic algorithm in the fitting procedure that really reduces time consuming compared to the direct scanning method.
    No preview · Article · Mar 2011 · Computational and Theoretical Chemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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 (LPA(1)), LPA(2), LPA(3), LPA(4), LPA(5) and LPA(6). 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.
    Full-text · Article · Sep 2011 · Journal of Toxicologic Pathology
Show more