Evidence for downregulation of the negative regulator SPRED2 in clinical prostate cancer

N Kachroo1, T Valencia, A Y Warren

  • 1Translational Prostate Cancer Group, Hutchison/MRC Research centre, University of Cambridge, Cambridge CB1 0XZ, UK.

British Journal of Cancer
|November 22, 2012
PubMed
Abstract

Insights

SPRED2, a negative regulator of MAPK signaling, is downregulated in prostate cancer. Its reduced expression correlates with higher tumor grade and promotes cancer cell proliferation, suggesting it may act as a tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • SPRED1 and SPRED2 are negative regulators of MAPK signaling in mammalian cells.
  • Investigating the role of SPRED proteins in prostate cancer progression.

Purpose of the Study:

  • To investigate the expression and functional role of SPRED1 and SPRED2 in prostate cancer.
  • To determine if SPRED2 acts as a tumor suppressor in prostate cancer.

Main Methods:

  • Transcriptome analysis of microdissected, grade-specific prostate cancers.
  • In vitro functional assays to assess the effect of SPRED2 manipulation on cancer cell behavior.

Main Results:

  • SPRED2 mRNA was downregulated in prostate tumors compared to benign glands, with greater downregulation in higher-grade tumors.
  • SPRED2 overexpression inhibited prostate cancer cell proliferation and migration.
  • SPRED2 suppression enhanced prostate cancer cell proliferation and migration.

Conclusions:

  • SPRED2 is downregulated in prostate cancer, particularly in higher-grade tumors.
  • SPRED2 functions as a negative regulator of prostate cancer cell proliferation and migration.
  • SPRED2 warrants further investigation as a potential tumor suppressor gene in prostate cancer.