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

  • Authors:
    • Lee Lee Wong
    • Chan Fong Chang
    • Evelyn S.C. Koay
    • Daohai Zhang
  • View Affiliations

  • Published online on: May 1, 2009     https://doi.org/10.3892/ijo_00000256
  • Pages: 1291-1301
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Abstract

Activation of HER-2/neu leads to multiple signalling cascades and plays a vital role in cell survival and growth. We used a signal transduction antibody array to characterize the tyrosine phosphorylation profiles in heregulin (HRG α1)-treated BT474 breast cancer cells, and identified a group of 80 molecules in which tyrosine phosphorylation was highly regulated by HRG-enhanced HER-2/neu signalling. These phosphoproteins included many known HER-2/neu-regulated molecules (e.g., SHC, Akt, Syk and Stat1) and proteins that had not been previously linked to HER-2/neu signalling, such as Fas-associated death domain protein (FADD), apoptosis repressor with CARD domain (ARC), and the tumour suppressor, protein phosphatase type 2A (PP2A). Pharmacological inhibition with HER-2 inhibitor AG825, PI3K inhibitor LY294002, MEK1/2 inhibitor PD98095, and p38MAPK inhibitor SB203580 confirmed that PP2A phosphorylation was modulated by the complicated, HER-2/neu-driven downstream signal network, with the PI3K and MEK1/2 positively, while the p38MAPK negatively regulating its tyrosine phosphorylation. In breast tumour specimens, expression of tyrosine-phosphorylated PP2A (pY307-PP2A) was highly increased in the HER-2/neu positive breast tumours, and significantly correlated to tumour progression, thus enhancing its potential prognostic value. Our data provide meaningful information in the elucidation of the HER-2-driven tyrosine phosphorylation network, and in the development of phosphopeptide-related targets as prognostication indicators.

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May 2009
Volume 34 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wong LL, Chang CF, Koay ES and Zhang D: Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression. Int J Oncol 34: 1291-1301, 2009.
APA
Wong, L.L., Chang, C.F., Koay, E.S., & Zhang, D. (2009). Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression. International Journal of Oncology, 34, 1291-1301. https://doi.org/10.3892/ijo_00000256
MLA
Wong, L. L., Chang, C. F., Koay, E. S., Zhang, D."Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression". International Journal of Oncology 34.5 (2009): 1291-1301.
Chicago
Wong, L. L., Chang, C. F., Koay, E. S., Zhang, D."Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression". International Journal of Oncology 34, no. 5 (2009): 1291-1301. https://doi.org/10.3892/ijo_00000256