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

在妊娠着床期，正常的滋养细胞表现得像恶性细胞一样，表现出快速的生长能力和侵入子宫内膜的能力。可能是多种致癌基因导致了正常滋养细胞的这些恶性样表型。由于人绒毛膜癌细胞通常保留正常滋养细胞的多种特征，我们将病毒H-或K-ras癌基因转染到人绒毛膜癌细胞系CC1中，并分析了表达活化ras癌基因的CC1细胞的生物学特性。所有表达h -ras的无性系均明显形成半球形，而表达k -ras的无性系和对照无性系均不形成半球形。显微镜观察表明，这些穹窿是细胞层与培养皿表面之间积聚的充满液体的空腔。扫描电镜显示穹窿细胞形态与胚泡相似。此外，Na^+-K^+-ATPase活性在h -ras表达的克隆中显著升高。用一种特殊的Na^+-K^+- atp酶抑制剂瓦巴因治疗后，这些圆顶在24小时内变平。接下来，我们检查了人绒毛膜促性腺激素（hCG）的产生。表达k -ras的克隆比表达h -ras的克隆和对照细胞分泌更多的hCG。在本研究中，我们发现ras癌基因深度参与滋养细胞的主动转运和hCG分泌。

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.