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Published on: July 17, 2020

Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression

Lee Lee Wong1, Chan Fong Chang, Evelyn S C Koay

  • 1Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074.

International Journal of Oncology
|April 11, 2009
PubMed

Insights

Heregulin (HRG alpha1) activates HER-2/neu signaling, altering tyrosine phosphorylation in breast cancer cells. Increased tyrosine-phosphorylated protein phosphatase type 2A (pY307-PP2A) in HER-2/neu positive tumors correlates with progression, suggesting prognostic value.

Area of Science:

  • Oncology
  • Molecular Biology
  • Signal Transduction

Background:

  • HER-2/neu signaling is crucial for cell survival and growth in breast cancer.
  • Understanding the downstream signaling network is vital for targeted therapies and prognostication.

Purpose of the Study:

  • To characterize the tyrosine phosphorylation profiles regulated by heregulin (HRG alpha1)-enhanced HER-2/neu signaling in breast cancer cells.
  • To investigate the role of protein phosphatase type 2A (PP2A) in this network and its potential as a prognostic marker.

Main Methods:

  • Utilized a signal transduction antibody array to analyze phosphoprotein profiles in HRG alpha1-treated BT474 cells.
  • Employed pharmacological inhibitors (AG825, LY294002, PD98095, SB203580) to dissect signaling pathways.
  • Examined tyrosine-phosphorylated PP2A (pY307-PP2A) expression in breast tumor specimens.

Main Results:

  • Identified 80 molecules with regulated tyrosine phosphorylation, including known and novel HER-2/neu targets like FADD, ARC, and PP2A.
  • Confirmed PI3K and MEK1/2 positively regulate PP2A phosphorylation, while p38MAPK negatively regulates it within the HER-2/neu network.
  • Found significantly increased pY307-PP2A in HER-2/neu positive tumors, correlating with tumor progression.

Conclusions:

  • Elucidated key components of the HER-2/neu-driven tyrosine phosphorylation network.
  • Demonstrated that pY307-PP2A is a potential prognostic indicator in HER-2/neu positive breast cancer.
  • Highlighted the complex interplay of signaling pathways in regulating PP2A phosphorylation.

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