Stable expression of activated Ki-Ras does not constitutively activate the mitogen-activated protein kinase pathway but attenuates epidermal growth factor receptor activation in human astrocytoma cells.

  • Authors:
    • W Luo
    • M Sharif
  • View Affiliations

  • Published online on: January 1, 1999     https://doi.org/10.3892/ijo.14.1.53
  • Pages: 53-115
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Abstract

Mutation in the ras oncogene is one of the most commonly reported genetic aberrations in human cancer. Activated ras mutants are thought to play a major role in promoting the growth and malignancy of tumor cells. Ras protein plays a central role in transmitting mitogenic signals from cell surface-to-nucleus by activating signaling pathways in response to receptor activation. Ras protein by recruiting c-Raf-1 kinase to the plasma membrane activates the mitogen-activated protein (MAP) kinase pathway. Expression of activated ras mutants in rodent fibroblast has been reported to constitutively activate the MAP kinase pathway, suggesting that constitutive activation of this pathway contributes to Ras influence on proliferation and transformation. In this study, we investigated whether stable expression of an activated Ki-Ras oncogenic mutant (G12V) in human astrocytoma cells leads to constitutive activation of the MAP kinase pathway and how this may influence cellular proliferation and signaling by epidermal growth factor (EGF) receptor. We discovered that Ki-Ras stable expression does not lead to constitutive activation of the MAP kinase pathway, rather expression of Ki-Ras plays a role in attenuating the activation of this pathway in response to EGF stimulation. Furthermore, we provide evidence that stable Ki-Ras expression attenuates the ability of EGF receptor to activate the MAP kinase pathway by interfering with the receptor ability to autophosphorylate at tyrosine residues and not by down regulating receptor expression.

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Jan 1999
Volume 14 Issue 1

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

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Spandidos Publications style
Luo W and Luo W: Stable expression of activated Ki-Ras does not constitutively activate the mitogen-activated protein kinase pathway but attenuates epidermal growth factor receptor activation in human astrocytoma cells.. Int J Oncol 14: 53-115, 1999
APA
Luo, W., & Luo, W. (1999). Stable expression of activated Ki-Ras does not constitutively activate the mitogen-activated protein kinase pathway but attenuates epidermal growth factor receptor activation in human astrocytoma cells.. International Journal of Oncology, 14, 53-115. https://doi.org/10.3892/ijo.14.1.53
MLA
Luo, W., Sharif, M."Stable expression of activated Ki-Ras does not constitutively activate the mitogen-activated protein kinase pathway but attenuates epidermal growth factor receptor activation in human astrocytoma cells.". International Journal of Oncology 14.1 (1999): 53-115.
Chicago
Luo, W., Sharif, M."Stable expression of activated Ki-Ras does not constitutively activate the mitogen-activated protein kinase pathway but attenuates epidermal growth factor receptor activation in human astrocytoma cells.". International Journal of Oncology 14, no. 1 (1999): 53-115. https://doi.org/10.3892/ijo.14.1.53