Expression of Transforming Growth Factor-beta Receptors and Related Cell-Cycle Components in Transitional-Cell

McGarvey1, Tait, Tomaszewski

  • 1Department of Surgery, Division of Urology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.

Molecular Urology
|June 14, 2000
PubMed

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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