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Published on: August 22, 2010

Expression profile of Rho kinases in urinary bladder cancer

D Volanis1, A Zaravinos, T Kadiyska

  • 1Department of Clinical Virology, University of Crete, Heraklion, Crete, Greece.

Journal of B.U.ON. : Official Journal of the Balkan Union of Oncology
|October 19, 2011
PubMed
Abstract

Insights

RhoB is downregulated in urothelial cell carcinoma (UCC), suggesting a tumor-suppressor role, while other Rho kinases are upregulated, impacting UCC development and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Urothelial cell carcinoma (UCC) is the most common type of bladder cancer.
  • Rho GTPases are critical regulators of the actin cytoskeleton, cell migration, and proliferation.
  • Dysregulation of Rho GTPase signaling pathways is implicated in various cancers.

Purpose of the Study:

  • To investigate the expression of RhoA, RhoB, RhoC, Rac1, and Cdc42 kinases in UCC.
  • To determine the expression profile of 107 Rho-associated genes in UCC.
  • To correlate Rho kinase expression with clinical outcomes in UCC patients.

Main Methods:

  • Expression analysis using microarrays, quantitative PCR (qPCR), and Western blotting.
  • Analysis of 77 UCC specimens with paired normal urothelium.
  • Computational analysis of Gene Expression Omnibus (GEO) datasets.

Main Results:

  • RhoB mRNA and protein levels were significantly decreased in UCC, indicating a tumor-suppressor function.
  • RhoA, RhoC, and Cdc42 protein levels were significantly elevated in UCC.
  • High Cdc42 mRNA expression correlated with poorer overall survival, while high RhoB mRNA expression correlated with better survival.

Conclusions:

  • The majority of Rho-related genes are overexpressed in UCC compared to normal tissue.
  • Aberrant expression of RhoA, RhoB, RhoC, Rac1, and Cdc42 is crucial in the initiation and progression of UCC.
  • Rho GTPase signaling represents a potential therapeutic target for bladder cancer.

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