TY - JOUR
T1 - The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model
AU - Pons, Berta
AU - Peg, Vicente
AU - Vázquez-Sánchez, María Ángeles
AU - López-Vicente, Laura
AU - Argelaguet, Elisabet
AU - Coch, Laura
AU - Martínez, Alba
AU - Hernández-Losa, Javier
AU - Armengol, Gemma
AU - Ramon Y Cajal, Santiago
N1 - Ramon y Cajal, S. and Armengol, G. shared senior authorship
PY - 2011/11/1
Y1 - 2011/11/1
N2 - 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.
AB - 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.
KW - 4E-binding protein 1
KW - Breast cancer
KW - E-cadherin
KW - Eukaryotic initiation factor 4E
KW - Protein translation
KW - β-catenin
U2 - 10.3892/ijo.2011.1118
DO - 10.3892/ijo.2011.1118
M3 - Article
SN - 1019-6439
VL - 39
SP - 1337
EP - 1345
JO - International Journal of Oncology
JF - International Journal of Oncology
ER -