The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model
Pons López, Berta (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Peg, Vicente (Hospital Universitari Vall d'Hebron)
Vázquez-Sánchez, María Ángeles (Hospital Universitari Vall d'Hebron)
López-Vicente, Laura (Hospital Universitari Vall d'Hebron)
Argelaguet, Elisabet (Hospital Universitari Vall d'Hebron)
Coch, Laura (Hospital Universitari Vall d'Hebron)
Martínez, Alba (Hospital Universitari Vall d'Hebron)
Hernandez-Losa, Javier (Hospital Universitari Vall d'Hebron)
Armengol, Gemma (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)
Ramón y Cajal, Santiago (Hospital Universitari Vall d'Hebron)

Data:	2011
Resum:	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.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2005/SGR-00144 Fundació la Marató de TV3 052710
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	4E-binding protein 1 ; Breast cancer ; E-cadherin ; Eukaryotic initiation factor 4E ; Protein translation ; Β-catenin ; SDG 3 - Good Health and Well-being
Publicat a:	International Journal of Oncology, Vol. 39, issue 5 (Novmber 2011) , p. 1337-1345, ISSN 1791-2423

DOI: 10.3892/ijo.2011.1118

9 p, 679.3 KB

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