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Notch-1 signaling is lost in prostate adenocarcinoma and promotes PTEN gene expression

Jarrett T Whelan1, Anne Kellogg, Brian M Shewchuk

  • 1Division of Hematology/Oncology, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.

Journal of Cellular Biochemistry
|May 30, 2009
PubMed

Insights

Loss of Notch-1 signaling in prostate adenocarcinoma correlates with reduced PTEN tumor suppressor gene expression. Restoring Notch-1 activity increases PTEN, suggesting a role in prostate cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Prostate tumorigenesis is linked to decreased PTEN gene expression.
  • PTEN regulation by Notch-1 signaling has been recently reported.
  • Alterations in Notch-1 signaling may contribute to prostate adenocarcinoma development.

Purpose of the Study:

  • To investigate alterations in the Notch-1 signaling pathway in human prostate adenocarcinoma.
  • To determine if Notch-1 signaling regulates PTEN gene expression in prostate cells.

Main Methods:

  • Immunohistochemistry to assess cleaved Notch-1 protein in tumor and benign prostate tissues.
  • Analysis of Hey-1 expression to confirm Notch-1 signaling status.
  • Retroviral expression of active Notch-1 and ligand (Delta) incubation in prostate cell lines.
  • Chromatin immunoprecipitation to identify transcription factor binding to the PTEN promoter.

Main Results:

  • Prostate adenocarcinoma showed reduced cleaved Notch-1 and Hey-1 expression compared to benign tissue.
  • Active Notch-1 expression or Delta ligand stimulation increased PTEN gene expression in prostate cell lines.
  • CBF-1 was found to bind to the PTEN promoter region.

Conclusions:

  • Defects in Notch-1 signaling are present in human prostate adenocarcinoma.
  • Notch-1 signaling regulates PTEN tumor suppressor gene expression in prostate cells.
  • Impaired Notch-1 signaling may contribute to prostate tumor formation via PTEN regulation.

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