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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Published on: April 26, 2017

RREB1 transcription factor splice variants in urologic cancer

Matthew D Nitz1, Michael A Harding, Steven C Smith

  • 1Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.

The American Journal of Pathology
|June 28, 2011
PubMed

Insights

Ras and cancer-linked transcription factor RREB1 (Ras-responsive element-binding protein 1) has newly identified isoforms. RREB1β isoform may be required for bladder cancer cell proliferation, unlike RREB1α.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Ras-responsive element-binding protein 1 (RREB1) is a transcription factor involved in Ras signaling and cancer.
  • Limited knowledge exists regarding RREB1 isoform expression in cell lines and human tumors, and their clinical significance.

Purpose of the Study:

  • To develop tools for characterizing RREB1 protein and mRNA expression, including isoform-specific analysis.
  • To investigate the expression and clinical relevance of RREB1 isoforms in bladder and prostate cancer.
  • To explore the functional role of RREB1 isoforms in cancer cell proliferation.

Main Methods:

  • Development of immunohistochemistry (IHC) tools for RREB1 protein detection.
  • Establishment of methods for RREB1 mRNA amplification and isoform-specific knockdown.
  • Analysis of RREB1 expression in bladder and prostate cancer cell lines and human tissue samples.
  • In vitro proliferation assays using bladder cancer cell lines with selective RREB1 isoform knockdown.

Main Results:

  • Identification of previously known RREB1 splice variants (α, β, γ, δ) and a novel variant (ε).
  • Generally lower total and isoform-specific RREB1 mRNA expression in tumors compared to normal tissues.
  • No correlation found between total RREB1 expression and overall survival in bladder cancer patients.
  • RREB1α knockdown did not affect proliferation, but RREB1β knockdown inhibited proliferation in UMUC-3 bladder cancer cells.

Conclusions:

  • New reagents and methods for RREB1 isoform analysis have been developed.
  • RREB1 isoform expression patterns in cancer tissues are characterized.
  • RREB1β isoform may play a crucial role in bladder cancer cell proliferation, suggesting isoform-specific functions in carcinogenesis and progression.

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