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RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family

Kristin Eckfeld1, Luke Hesson, Michele D Vos

  • 1Department of Cell and Cancer Biology, National Cancer Institute, Rockville, Maryland 20850, USA.

Cancer Research
|December 3, 2004
PubMed

Insights

Researchers identified RASSF4, a new Ras effector and tumor suppressor. This protein induces apoptosis and inhibits tumor growth, but is often silenced in cancer cells.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Activated Ras proteins are key regulators of cell growth and transformation.
  • Ras effector proteins mediate diverse biological outcomes, including growth inhibition.
  • The RASSF (Ras association domain family) is a group of Ras effector/tumor suppressors.

Purpose of the Study:

  • To identify and characterize novel members of the RASSF family.
  • To investigate the role of RASSF4 as a Ras effector and potential tumor suppressor.

Main Methods:

  • Protein interaction assays (GTP-dependent binding to K-Ras).
  • Gene expression analysis (broad expression in normal tissues).
  • Functional assays (overexpression in 293-T cells and human tumor cell lines).
  • Epigenetic analysis (promoter methylation in tumor cells).

Main Results:

  • A fifth RASSF family member, RASSF4, was identified.
  • RASSF4 directly binds activated K-Ras in a GTP-dependent manner.
  • RASSF4 overexpression induces Ras-dependent apoptosis and inhibits tumor cell growth.
  • RASSF4 is frequently down-regulated in human tumors due to promoter methylation.

Conclusions:

  • RASSF4 is a novel Ras effector and a potential tumor suppressor.
  • RASSF4's growth-inhibitory functions are mediated through Ras signaling.
  • RASSF4 inactivation by promoter methylation contributes to tumorigenesis.

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