Role of RAS oncogenes in a human chorionic cancer cell line.

在妊娠的着床期，正常的滋养层细胞表现得像恶性细胞，显示出快速生长能力和侵入子宫内膜的能力。正常滋养层细胞的恶性表型可能与多种癌基因有关。由于人绒毛膜癌细胞通常保留了正常滋养层细胞的多样性特征，我们将病毒H-或K-ras癌基因转染到人绒毛膜癌细胞系CC 1中，并分析了表达激活的ras癌基因的CC 1细胞的生物学特性。所有表达H-ras的克隆都形成了独特的半球形圆顶，但K-ras表达克隆和对照克隆都没有。显微镜下观察发现，这些圆顶是充满液体的空腔，积聚在细胞层和培养皿表面之间。扫描电镜显示穹隆细胞形态类似于囊胚。此外，Na^+-K^+-ATP酶活性在H-ras表达克隆中显著更高。在用Na^+-K^+-ATP酶的特异性抑制剂哇巴因处理后24小时内，这些圆顶变平。接下来，我们检查了人绒毛膜促性腺激素（hCG）的产生。K-ras表达克隆分泌的hCG显著高于H-ras表达克隆和对照细胞。

During an implantation period of pregnancy, normal trophoblasts behave like malignant cells showing rapid growth capacity and invasiveness into the uterine endometrium. Probably a variety of oncogenes contribute to those malignant-like phenotypes of the normal trophoblasts. Since human choriocarcinoma cells generally preserve the diverse characterictics of normal trophoblasts, we transfected the viral H- or K-ras oncogene into a a human choriocarcinoma cell line, CC1, and analyzed the biological properties of CC1 cells expressing an activated ras oncogene. All H-ras-expressing clones distinctively formed the hemisherical domes, but none of K-ras-expressing clones and control clones did. Microscopic observation demonstrated that those domes were cavities filled with fluid which accumulated between the cell layr and the surface of culture dish. Scanning electron microscopy revealed that the dome cells were morphologicaly similar to a blastcyst. Furthermore, Na^+-K^+-ATPase activity activity was significantly higher in the H-ras-expressing clones. Those domes flattened within 24 hours after treatment with a specific inhibitor of Na^+-K^+-ATPase, ouabain. Next, we examined the production of human chorionic gonadotropin (hCG). K-ras-expressing clones secreted significantlt more hCG than H-ras-expressing clones and control cells.In the present study, we showed that ras oncogenes are profoundly involved in the active transport and the hCG secretion of trophoblasts.