Biosynthesis and secretion of growth factor proteins by kidney cells from DES-treated Syrian hamsters

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.