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Updated: Aug 7, 2026

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 31, 2013
Expression of Transforming Growth Factor-beta Receptors and Related Cell-Cycle Components in Transitional-Cell
1Department of Surgery, Division of Urology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
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.
Insights
Transforming growth factor-beta (TGF-beta) insensitivity in bladder cancer is linked to altered gene expression. Invasive tumors show decreased p27(KIP1) and TGF-beta receptor II, and increased cyclin E, contributing to cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Transforming growth factor-beta (TGF-beta) normally inhibits epithelial cell growth.
- Transitional-cell carcinoma (TCC) of the bladder often shows resistance to TGF-beta.
- Reduced TGF-beta1 and absent TGF-beta2 transcripts are observed in advanced TCCs.
Purpose of the Study:
- To investigate the expression of TGF-beta receptor I, TGF-beta receptor II, p27(KIP1), and cyclin E in normal bladder tissue and TCC.
- To understand the role of TGF-beta downstream targets in TCC's resistance to TGF-beta.
- To correlate gene expression changes with TCC invasiveness.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used.
- Gene expression levels of TGF-beta receptor I, TGF-beta receptor II, p27(KIP1), and cyclin E were analyzed.
- Samples included normal bladder mucosa, superficial TCC, and invasive TCC.
Main Results:
- p27(KIP1), TGF-beta receptors, and cyclin E mRNA levels were similar in superficial TCC and normal bladder.
- Invasive TCC showed significantly decreased p27(KIP1) and TGF-beta receptor II mRNA expression.
- Invasive TCC exhibited significantly increased cyclin E mRNA expression compared to superficial TCC and normal bladder.
Conclusions:
- Aberrant expression of p27(KIP1), TGF-beta receptor II, and cyclin E is associated with invasive bladder cancer.
- These molecular changes likely contribute to TCC's insensitivity to TGF-beta and its aggressive phenotype.
- Understanding these pathways may offer therapeutic targets for advanced bladder cancer.
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