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

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

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33 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1337-1345
JournalInternational Journal of Oncology
Publication statusPublished - 1 Nov 2011


  • 4E-binding protein 1
  • Breast cancer
  • E-cadherin
  • Eukaryotic initiation factor 4E
  • Protein translation
  • β-catenin


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