The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model

  • Authors:
    • Berta Pons
    • Vicente Peg
    • María Ángeles Vázquez-Sánchez
    • Laura López-Vicente
    • Elisabet Argelaguet
    • Laura Coch
    • Alba Martínez
    • Javier Hernández-Losa
    • Gemma Armengol
    • Santiago Ramon y Cajal
  • View Affiliations

  • Published online on: July 8, 2011     https://doi.org/10.3892/ijo.2011.1118
  • Pages: 1337-1345
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Abstract

Cell signaling pathways and protein translation are crucial for understanding malignant transformation. 4E-BP1 and the eIF4F complex regulate cap-dependent translation. We investigated how 4E-BP1 and eIF4E phosphorylation status affects in vitro and in vivo cell proliferation in a breast cancer model. Cells from 2 breast carcinoma lines (MDA-MB 231 and MDA-MB 468) and human fibroblasts (IMR90 cells) were infected in vitro with a retrovirus carrying a wild-type 4E-BP1 or a mutant 4E-BP1 unable to hyperphosphorylate. Overexpression of the mutant 4E-BP1 induced a significant decrease in cell proliferation in IMR90 and MDA-MB 468 cells, but not in MDA-MB 231 cells. A correlation was observed between baseline-phosphorylated eIF4E (p-eIF4E) levels and sensitivity to 4E-BP1 transduction. By co-immunoprecipitation, p-eIF4E seemed to present lower affinity for 4E-BP1 than total eIF4E in MDA-MB 468 cells. After treatment with CGP57380, the MAP kinase-interacting kinase (MNK) inhibitor, downregulation of p-eIF4E levels was associated with an increase of E-cadherin and β-catenin protein expression. These results provide evidence that 4E-BP1 transduction leads to a decrease in cell proliferation, and that high p-eIF4E levels may counteract the suppressor effect of 4E-BP1. We propose that high p-4E-BP1 and p-eIF4E levels are central factors in cell signaling and reflect the oncogenic potential of cell signaling pathways in breast cancer.

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November 2011
Volume 39 Issue 5

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

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APA
Pons, B., Peg, V., Vázquez-Sánchez, M.Á., López-Vicente, L., Argelaguet, E., Coch, L. ... Ramon y Cajal, S. (2011). The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. International Journal of Oncology, 39, 1337-1345. https://doi.org/10.3892/ijo.2011.1118
MLA
Pons, B., Peg, V., Vázquez-Sánchez, M. Á., López-Vicente, L., Argelaguet, E., Coch, L., Martínez, A., Hernández-Losa, J., Armengol, G., Ramon y Cajal, S."The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model". International Journal of Oncology 39.5 (2011): 1337-1345.
Chicago
Pons, B., Peg, V., Vázquez-Sánchez, M. Á., López-Vicente, L., Argelaguet, E., Coch, L., Martínez, A., Hernández-Losa, J., Armengol, G., Ramon y Cajal, S."The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model". International Journal of Oncology 39, no. 5 (2011): 1337-1345. https://doi.org/10.3892/ijo.2011.1118