Expression of transforming growth factor β1 and its receptors in normal human urothelium and human transitional cell carcinomas

Abstract

Previous studies indicated that transforming growth factor β 1 (TGFβ 1) is expressed by normal urothelial cells and exerts regulatory autocrine functions in urothelial maintenance and wound healing. However, little is known about the expression patterns of TGFβ 1 and its receptors in bladder tumors. Therefore, we studied the protein and mRNA localization of TGFβ 1 and TGFβ receptor types I and II (TGFβRI and TGFβRII) in normal human urothelium and transitional cell carcinomas (TCCs) of different grades and stages. Expression of TGFβ 1 and its receptors was examined by immunocytochemistry and mRNA in situ hybridization in normal urothelium and TCCs using a semiquantitative method. By immunocytochemistry, the expression of TGFβ 1 and TGFβRII was higher in superficial and basal cell layers of normal urothelium than in the intermediate layer. A similar localization was seen in superficial TCCs. TGFβRI was mainly present in basal and intermediate cell layers of normal urothelium and superficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells stained intensely for all three proteins. No correlation was found between immunostaining and TCC grade. In situ hybridization pointed out that all cell layers in normal urothelium exhibit similar TGFβ 1 mRNA levels. Elevated TGFβ 1 mRNA levels were noted in TCCs irrespective of grade or stage. In conclusion, these data indicate that in normal urothelium TGFβ 1, TGFβRI, and TGFβRII expression depend on maturation and differentiation. This pattern is particularly lost in muscle invasive TCCs, in which the expression of the three proteins is enhanced. These data suggest autocrine TGFβ 1 mechanisms in human TCC cells that may be more pronounced in muscle invasive TCC cells.