The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis

Davide Ruggero; Lorenzo Montanaro; Li Ma; Wei Xu; Paola Londei; Carlos Cordon-Cardo; Pier Paolo Pandolfi

doi:10.1038/nm1042

The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis

Nat Med. 2004 May;10(5):484-6. doi: 10.1038/nm1042. Epub 2004 Apr 18.

Authors

Davide Ruggero¹, Lorenzo Montanaro, Li Ma, Wei Xu, Paola Londei, Carlos Cordon-Cardo, Pier Paolo Pandolfi

Affiliation

¹ Cancer Biology and Genetics Program, and Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

PMID: 15098029
DOI: 10.1038/nm1042

Abstract

The mammalian target of rapamycin, mTOR, regulates cell growth and proliferation. Here we show that the initiation factor of translation (eIF-4E), a downstream effector of mTOR, has oncogenic effects in vivo and cooperates with c-Myc in B-cell lymphomagenesis. We found that c-Myc overrides eIF-4E-induced cellular senescence, whereas eIF-4E antagonizes c-Myc-dependent apoptosis in vivo. Our results implicate activation of eIF-4E as a key event in oncogenic transformation by phosphoinositide-3 kinase and Akt.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Apoptosis
Cocarcinogenesis
Eukaryotic Initiation Factor-4E / genetics
Eukaryotic Initiation Factor-4E / physiology*
Gene Expression
Genes, myc*
Lymphoma, B-Cell / etiology*
Lymphoma, B-Cell / genetics
Lymphoma, B-Cell / pathology
Mice
Mice, Transgenic
Protein Kinases / physiology
TOR Serine-Threonine Kinases

Substances

Eukaryotic Initiation Factor-4E
Protein Kinases
mTOR protein, mouse
TOR Serine-Threonine Kinases