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HER-2/neu (erbB-2) and the cell cycle

D Busse1, R S Doughty, C L Arteaga

  • 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

Seminars in Oncology
|March 10, 2001
PubMed

Insights

HER-2 proto-oncogene signaling activates pathways affecting cell cycle regulators, potentially driving cancer. Targeting HER-2 may require reversing these effects, with cyclin D1 and p27KIP1 implicated in cell cycle disruption.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • HER-2 proto-oncogene amplification and overexpression are linked to various cancers.
  • HER-2 signaling influences cell cycle progression, contributing to cellular transformation.
  • Therapeutic strategies targeting HER-2 require understanding its impact on cell cycle regulation.

Purpose of the Study:

  • To investigate the role of HER-2 signaling in modulating cell cycle regulators.
  • To identify specific molecules involved in HER-2-mediated cell cycle subversion.
  • To explore potential mechanisms for reversing HER-2 effects for therapeutic benefit.

Main Methods:

  • Analysis of signaling pathways activated by HER-2.
  • Examination of the expression and function of cell cycle regulators.
  • Investigation of the involvement of cyclin D1 and p27KIP1 in HER-2 signaling.

Main Results:

  • HER-2 signaling activates biochemical pathways that alter cell cycle regulators.
  • These alterations are critical for the transformed phenotype associated with HER-2.
  • Cyclin D1 and p27KIP1 appear to be involved in disrupting the G1/S cell cycle transition via HER-2 pathways.

Conclusions:

  • HER-2 signaling profoundly impacts cell cycle control, promoting cancer phenotypes.
  • Understanding these molecular alterations is crucial for effective HER-2 targeted therapies.
  • Cyclin D1 and p27KIP1 are key players in HER-2-driven cell cycle dysregulation.

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