Elevated Levels of Glucose Transport and Transporter Messenger RNA Are Induced by <i>ras</i> or <i>src</i> Oncogenes

TLDR

Accelerated glucose transport is a hallmark of cellular transformation. The study investigates how activated oncogenes alter glucose transporter activity in cultured rodent fibroblasts. Researchers transfected rodent fibroblasts with activated myc, ras, or src oncogenes to examine changes in transporter activity. Activated ras and src oncogenes, and the tumor promoter TPA, all markedly increased glucose uptake, transporter protein, and mRNA, showing that upregulation of the transporter gene drives the enhanced transport.

Abstract

An accelerated rate of glucose transport is among the most characteristic biochemical markers of cellular transformation. To study the molecular mechanism by which transporter activity is altered, cultured rodent fibroblasts transfected with activated myc , ras , or src oncogenes were used. In myc -transfected cells, the rate of 2-deoxy-D-glucose uptake was unchanged. However, in cells transfected with activated ras and src oncogenes, the rate of glucose uptake was markedly increased. The increased transport rate in ras - and src -transfected cells was paralleled by a marked increase in the amount of glucose transporter protein, as assessed by immunoblots, as well as by a markedly increased abundance of glucose transporter messenger RNA. Exposure of control cells to the tumor-promoting phorbol ester 12- O -tetradecanoyl phorbol-13-acetate (TPA) for 18 hours had a similar effect of increasing the rate of glucose transport and the abundance of transporter messenger RNA. For ras , src , and TPA, the predominant mechanism responsible for activation of the transport system is increased expression of the structural gene encoding the glucose transport protein.