Ståhle-Bäckdhal M, Inoue M, Zedenius J, Sandstedt B, DeMarco L, Flam F, Silfverswärd C, Andrade J, Friedman E
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Am J Pathol. 1995 May;146(5):1073-8.
The normally developing placenta undergoes extensive but regulated noninvasive cellular proliferation. Various proto-oncogenes and growth factors have been associated with the regulation of trophoblastic placental growth. Activation of some oncogenes and altered expression of growth factors have been demonstrated in trophoblastic tumors (hydatidiform mole and choriocarcinoma). The ras proto-oncogene plays a key role in the signal transduction cascade of activated growth factors, and is known to be activated or overexpressed in multiple tumor types. Ras GTPase activating protein (RasGAP), a major down-regulator of ras activity, is present at high levels in placenta. To assess the role that Ras-GAP plays in the development of trophoblastic tumors, we performed immunohistochemical analyses with anti RasGAP antibodies of normal placentas, hydatidiform moles, invasive moles, and malignant choriocarcinomas. Normal placentas and noninvasive hydatidiform mole displayed intense positive staining confined to trophoblasts, whereas no staining was observed in the trophoblasts of invasive moles or choriocarcinomas. Thus, there was an inverse correlation between expression levels of RasGAP protein and the invasive potential and malignant phenotype in human trophoblastic tumors. The data indicate that RasGAP may play a regulatory role in trophoblast proliferation and that abolishing its activity may be associated with malignant transformation of these cells.
正常发育的胎盘会经历广泛但受调控的非侵入性细胞增殖。多种原癌基因和生长因子与滋养层胎盘生长的调控有关。在滋养层肿瘤（葡萄胎和绒毛膜癌）中已证实某些原癌基因的激活和生长因子表达的改变。ras原癌基因在活化生长因子的信号转导级联反应中起关键作用，并且已知在多种肿瘤类型中被激活或过度表达。Ras GTP酶激活蛋白（RasGAP）是ras活性的主要下调因子，在胎盘中高水平存在。为了评估Ras - GAP在滋养层肿瘤发生发展中的作用，我们用抗RasGAP抗体对正常胎盘、葡萄胎、侵蚀性葡萄胎和恶性绒毛膜癌进行了免疫组化分析。正常胎盘和非侵入性葡萄胎在滋养层细胞中显示出强烈的阳性染色，而在侵蚀性葡萄胎或绒毛膜癌的滋养层细胞中未观察到染色。因此，RasGAP蛋白表达水平与人类滋养层肿瘤的侵袭潜能和恶性表型呈负相关。数据表明RasGAP可能在滋养层细胞增殖中起调节作用，其活性的丧失可能与这些细胞的恶性转化有关。
