Expression of transforming growth factor beta 1 and its receptors in normal human urothelium and human transitional cell carcinomas

Previous studies indicated that transforming growth factor beta(1) (TGF bet a(1)) is expressed by normal urothelial cells and exerts: regulatory autocr ine functions in urothelial maintenance and wound healing; However, little is known about the expression patterns of TGF beta(1) and its receptors in bladder tumors. Therefore, we studied the protein and mRNA localization of TGF beta(1) and TGF beta receptor types I and II (TGF beta RI and TGF beta RII) in normal human urothelium and transitional cell carcinomas (TCCs) of different grades and stages. Expression of TGF beta(1) and its receptors wa s examined by immunocytochemistry and mRNA in situ hybridization in normal urothelium and TCCs using a semiquantitative method. By immunocytochemistry , the expression of TGF beta(1) and TGF beta RII was higher in superficial and basal cell layers of normal urothelium than in the intermediate layer. A similar localization was seen in superficial TCCs. TGF beta RI was mainly present in basal and intermediate cell layers of normal urothelium and sup erficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells staine d intensely for all three proteins. No correlation was found between immuno staining and TCC grade. In situ hybridization pointed out that all cell lay ers in normal urothelium exhibit similar TGF beta(1) mRNA levels. Elevated TGF beta(1) mRNA levels were noted in TCCs irrespective of grade or stage. In conclusion, these data indicate that in normal urothelium TGF beta(1), T GF beta RI, and TGF beta RII expression depend on maturation and differenti ation. This pattern is particularly lost in muscle invasive TCCs, in which the expression of the three proteins is enhanced. These data suggest autocr ine TGF beta(1) mechanisms in human TCC cells that may be more pronounced i n muscle invasive TCC cells. Copyright (C) 1999 by W.B. Saunders Company.