ALTERED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA - AN EARLY EVENT IN RENAL-CELL CARCINOMA DEVELOPMENT

Transforming growth factor-alpha (TGF-alpha) is a multifunctional cell regulatory protein with a wide range of effects on cell growth and di fferentiation and has been implicated in the neoplastic transformation of a variety of cell types. Altered expression of TGF-alpha and its c ognate receptor (epidermal growth factor receptor) is enhanced in huma n and rat renal cell carcinomas. The objective of the study reported h ere was to determine whether altered TGF-alpha expression is an early or late event in renal tubular oncogenesis. The immunohistochemical ex pression of TGF-alpha was studied in preneoplastic renal tubular lesio ns in a rat model of hereditary renal cell carcinoma. Strong TGF-alpha immunoreactivity was present at all stages of renal cell tumor develo pment, including the earliest detectable dysplasias. In contrast, the non-neoplastic regenerating tubular epithelium of rat degenerative nep hropathy did not stain for TGF-alpha, although this tissue exhibited a proliferative capacity similar to that observed in the dysplastic and neoplastic lesions. This study indicated that altered TGF-alpha expre ssion was detectable early in the development of renal cell tumors and may be an important feature of the transformed phenotype. (C) 1997 Wi ley-Liss, Inc.