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.