Translation of ODC mRNA and Polyamine Transport Are Suppressed inras-Transformed CREF Cells by Depleting Translation Initiation Factor 4E

JR Graff, A De Benedetti, JW Olson, P Tamez… - Biochemical and …, 1997 - Elsevier
JR Graff, A De Benedetti, JW Olson, P Tamez, RA Casero Jr, SG Zimmer
Biochemical and biophysical research communications, 1997Elsevier
Rapid tumor growth and metastasis require increased polyamine metabolism, which is
coordinately regulated by ornithine decarboxylase (ODC) and the polyamine transporter.
Both activities are stimulated by ras signalling and are dependent upon protein biosynthesis.
T24rasoncogene expression in rat embryo fibroblasts (CREFT24) induces cellular
transformation and malignancy, in part, by stimulating the rate-limiting translation initiation
factor, eIF-4E. CREFT24 expressing antisense RNA to eIF-4E (AS4E) have markedly …
Rapid tumor growth and metastasis require increased polyamine metabolism, which is coordinately regulated by ornithine decarboxylase (ODC) and the polyamine transporter. Both activities are stimulated by ras signalling and are dependent upon protein biosynthesis. T24rasoncogene expression in rat embryo fibroblasts (CREFT24) induces cellular transformation and malignancy, in part, by stimulating the rate-limiting translation initiation factor, eIF-4E. CREFT24 expressing antisense RNA to eIF-4E (AS4E) have markedly decreased tumor growth rates and metastatic capacity, without altered monolayer growth rates. Herein, we demonstrate that in AS4E, ODC is translationally suppressed resulting in decreased ODC activity. Additionally, exogenous polyamine uptake is suppressed in AS4E cells indicating that AS4E can neither generate nor import the polyamines necessary to support rapid tumor growth. These data provide evidence that eIF-4E is the link between ras-induced malignancy and increased polyamine metabolism and support the hypothesis that eIF-4E plays a pivotal role in mediating ras-induced malignancy.
Elsevier