Expression of Transforming Growth Factor-beta Receptors and Related Cell-Cycle Components in Transitional-Cell Carcinoma of the Bladder.

Abstract

Exogenous transforming growth factor-beta (TGF-beta) is a potent inhibitor of normal epithelial cell growth but does not generally inhibit the growth of cell lines of transitional-cell carcinoma (TCC) of the bladder. In addition, a lack of the TGF-beta2 transcript and a marked reduction of the TGF-beta1 transcript have been reported in some high-stage TCCs. The purpose of this investigation was to examine the steady-state expression of TGF-beta receptor I and TGF-beta receptor II and a downstream target, p27(KIP1), as well as cyclin E in normal bladder and superficial and invasive TCC in order to better understand the role of TGF-beta downstream targets in TCC insensitivity to TGF-beta. Quantitative RT-PCR was employed to study the expression of TGF-beta receptor I and receptor II. p27(KIP1), and cyclin E in normal bladder and superficial and invasive TCC lesions. Steady-state levels of p27(KIP1), TGF-beta receptors, and cyclin E mRNAs were similar in superficial TCC samples and normal bladder mucosa. There was a significant decrease in p27(KIP1) and TGF-beta receptor II mRNA expression in invasive lesions compared with superficial tumors (P < 0.004; P < 0.02). In contrast, there was no significant difference in the expression of TGF-beta receptor I mRNA between normal bladder and superficial and invasive TCC. There was a significant increase in the expression of cyclin E mRNA in invasive TCC compared with superficial TCC or normal bladder (P < 0.015). These results suggest that aberrant expression of these genes contributes to the phenotype of invasive bladder cancer.