The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis.
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.
Ruggero
Davide
D
Cancer Biology and Genetics Program, and Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Montanaro
Lorenzo
L
Ma
Li
L
Xu
Wei
W
Londei
Paola
P
Cordon-Cardo
Carlos
C
Pandolfi
Pier Paolo
PP
D000818:Animals; D017209:Apoptosis; D003043:Cocarcinogenesis; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D016259:Genes, myc; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011494:Protein Kinases / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D039561:Eukaryotic Initiation Factor-4E; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases