Expression of Transforming Growth Factor-beta Receptors and Related Cell-Cycle Components in Transitional-Cell Carcinoma of the Bladder.
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.
McGarvey
TW
Department of Surgery, Division of Urology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
Tait
E
Tomaszewski
JE
Malkowicz
SB