[Roles of ras genes on biological properties of human choriocarcinoma cells].

Human choriocarcinoma cell lines, preserving many biological properties of normal trophoblasts, are good models for investigating of trophoblastic cell biology. Most of these cells express various oncogenes, which might have essential roles for biological characteristics of choriocarcinoma cells. Of these oncogenes, ras gene family has been known to play the key roles in cell growth, transformation and differentiation. In order to investigate the roles of ras genes on various unique characters of trophoblasts, the author transfected the viral H- or K-ras oncogene into a human choriocarcinoma cell line, CC1, and established choriocarcinoma cell lines acquired up-regulated activity of ras genes. v-ras-expressing clones exhibited almost the same growth capacities as control clones, but only v-H-ras clones formed the many fluid-filled hemispherical "domes" in a cell layer. Microscopic observation of these domes clarified that the accumulation of fluid between cell layer and the surface of culture dish has resulted in dome formation, which is characteristic of the polarized epithelial cells and represents an in vitro morphologic expression of vectorial transport function. Since these clones exhibited higher Na(+)-K(+)-ATPase activity than other clones and dome formation was inhibited with the treatment of ouabain, a specific inhibitor of Na(+)-K(+)-ATPase, dome formation may be due to the augmentation of the vectorial fluid transport driven by Na(+)-K(+)-ATPase. In addition, the expression of human chorionic gonadotropin (hCG) beta was examined to investigate the effects of ras genes on peptide hormone production which is one of the differentiated functions of trophoblasts. v-K-ras-expressing clones secreted significantly more hCG than controls, while v-H-ras did not seem to affect hCG-producing activity. These results obtained in this study indicate that H-ras gene may facilitate the vectorial transcellular fluid transport from maternal site to fetus, while K-ras gene is associated with some endocrine functions such as hCG production in trophoblasts.