Beleh M A, Brueggemeier R W, Chang G C, Lin Y C
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
Biochem Biophys Res Commun. 1993 Feb 15;190(3):1029-36. doi: 10.1006/bbrc.1993.1152.
Long-term estrogen treatment of Syrian hamsters results in the initiation and development of hormone-dependent renal adenocarcinomas. The pathway(s) to neoplastic transformation remain unknown in this animal model of hormonal carcinogenesis. In the present study, short-term primary kidney cell cultures and incubations of freshly prepared kidney slices have been incubated with [35S]-methionine to study the effects of estrogen treatment on protein biosynthesis in the Syrian hamster. An increase in amount of two secreted proteins were observed with an increasing duration of diethylstilbestrol (DES) treatment. Further characterization of these proteins by two-dimensional electrophoresis identified two proteins present only in treated hamsters, a 20-22 kDa protein and a 16-18 kDa protein with an isoelectric point of 8.5-9.0. Immunoprecipitation using specific antibodies to growth factors, followed by separation on SDS-PAGE electrophoresis, showed that kidney slices from five month-treated animals produced a TGF-alpha-like protein and a bFGF-like protein. The induction of these growth factors may play an important role in the tumorigenic process in kidneys of Syrian hamsters, including cell proliferation and vascularization of the tumor tissue.
对叙利亚仓鼠进行长期雌激素治疗会导致激素依赖性肾腺癌的发生和发展。在这种激素致癌动物模型中，肿瘤转化的途径尚不清楚。在本研究中，短期原代肾细胞培养物和新鲜制备的肾切片与[35S]-甲硫氨酸一起孵育，以研究雌激素处理对叙利亚仓鼠蛋白质生物合成的影响。随着己烯雌酚（DES）处理时间的延长，观察到两种分泌蛋白的量增加。通过二维电泳对这些蛋白质进行进一步表征，鉴定出仅在经处理的仓鼠中存在的两种蛋白质，一种20 - 22 kDa的蛋白质和一种等电点为8.5 - 9.0的16 - 18 kDa的蛋白质。使用针对生长因子的特异性抗体进行免疫沉淀，然后在SDS - PAGE电泳上分离，结果表明，经过五个月处理的动物的肾切片产生了一种TGF-α样蛋白和一种bFGF样蛋白。这些生长因子的诱导可能在叙利亚仓鼠肾脏的肿瘤发生过程中起重要作用，包括肿瘤组织的细胞增殖和血管形成。
