title: Frequent mutations of lysophosphatidic acid receptor-1 gene in rat liver tumors.
abstract: 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 LPA1 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 in rat liver carcinogenesis.
authors.affiliation: Department of Life Science, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Obo
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamada
authors.forename: Mami
authors.initials: M
authors.lastname: Furukawa
authors.forename: Mayuko
authors.initials: M
authors.lastname: Hotta
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D049368:Receptors, Lysophosphatidic Acid