Aberrant Expressions of Lysophosphatidic Acid Receptor Genes in Lung and Liver Tumors of Rats

Abstract

Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation and migration, and protects cells from apoptosis. It interacts with at least three specific G protein-coupled transmembrane receptors, LPA1, LPA2 and LPA3. In the present study, the involvement of LPA receptor genes in the development of rat tumors was evaluated by measuring mRNA expression of the LPA1, LPA2 and LPA3 genes in nitroso-compound induced lung adenocarcinomas and hepatocellular carcinomas (HCCs) in rats. Total RNA was extracted from 12 lung adenocarcinomas and 6 HCCs, and expression analysis was performed by real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). In lung adenocarcinomas, the expressions of LPA2 and LPA3 were significantly increased (p < 0.001 and p < 0.005, respectively) compared with normal lung tissue. In contrast, LPA1 showed a lower level of expression, but the difference was not significant. In HCCs, the expression of LPA2 was significantly increased (p < 0.05) compared with normal liver tissue. In contrast, varying levels of LPA1 and LPA3 expression were detected. The ratio of LPA2/LPA1, which is important for understanding the effects of LPA on target cells than the levels of LPA1 and LPA2 separately, increased markedly in both lung (p<0.005) and liver tumors (p<0.005). These results suggest that aberrant expressions of LPA receptors may be involved in the development of lung and liver tumors in the rat.