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Updated: Aug 9, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Effects of oncogenic ErbB2 on G1 cell cycle regulators in breast tumour cells

R M Neve1, H Sutterlüty, N Pullen

  • 1Friedrich Miescher Institute, Basel, Switzerland.

Oncogene
|April 14, 2000
PubMed

Insights

Functional inactivation of ErbB2 receptor tyrosine kinase in breast cancer cells halts tumor proliferation by disrupting ErbB3 signaling and cell cycle progression. c-Myc emerges as a key mediator of ErbB2

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • ErbB2 receptor tyrosine kinase overexpression drives proliferation in various human tumors.
  • Understanding ErbB2's oncogenic mechanisms is crucial for targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of ErbB2 in tumor proliferation by functionally inactivating the receptor.
  • To elucidate the downstream signaling pathways affected by ErbB2 inactivation.

Main Methods:

  • Utilized an engineered intracellular, ER-targeted single-chain antibody (scFv-5R) for inducible ErbB2 inactivation.
  • Assessed changes in ErbB2 localization, ErbB3, MAP kinase, PKB/Akt activity, and cell cycle progression (G1 phase, CDK2 activity).
  • Investigated the involvement of p27Kip1, c-Myc, and D-cyclins in ErbB2-mediated cell cycle control.

Main Results:

  • Inducible scFv-5R expression led to loss of plasma membrane ErbB2 and decreased activity of ErbB3, MAP kinase, and PKB/Akt.
  • ErbB2 inactivation caused G1 cell cycle arrest due to reduced CDK2 activity, mediated by p27Kip1 re-distribution.
  • Levels of c-Myc and D-cyclins decreased, and ectopic c-Myc expression partially rescued G1 arrest, indicating its role as a primary effector.

Conclusions:

  • Active ErbB2/ErbB3 dimers are essential for sustained kinase activity and tumor cell proliferation.
  • c-Myc is a key effector of ErbB2 oncogenicity, promoting cell cycle progression by antagonizing p27Kip1.
  • Targeting ErbB2 and its downstream effectors like c-Myc offers potential therapeutic strategies for ErbB2-overexpressing cancers.

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