Expression of the Farnesyltransferase β-Subunit Gene in Human Ovarian Carcinoma: Correlation to K-rasMutation

Abstract

Therassignaling protein requires a posttranslational modification to localize it to the inner surface of plasma membrane. In this state it can behave as a signal transduction mediator. Farnesyltransferase plays an important role in this posttranslational processing ofrasby attaching a farnesyl group to the cysteine of therasC-terminal tetrapeptide. In this study, we investigated the relationship of K-rasexpression and mutation with farnesyltransferase β-subunit expression in 20 ovarian tumors (17 carcinomas and 3 low malignant potential tumors) and 4 normal ovaries. The expression level of mRNA was determined by using quantitative PCR and mutation analysis was performed by direct cDNA sequencing. K-rasmutations were found in 1 of 3 low malignant potential tumors and in 4 of 17 carcinoma cases. K-rasmRNA overexpression was found in 1 of 3 low malignant potential tumors (one with mutatedras) and in only 1 of 17 carcinoma cases. Farnesyltransferase β-subunit mRNA overexpression was found in 2 of 3 low malignant potential tumors and in 7 of 17 carcinoma cases. Interestingly, all K-rasmutation cases showed farnesyltransferase β-subunit overexpression. These findings suggest that there may be a direct relationship between K-ras(rasdysfunction) mutation and expression of farnesyltransferase β-subunit gene.