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

  • Jeffrey S. Flier
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
  • Michael M. Mueckler
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
  • Patricia Usher
    The Charles A. Dana Research Institute and the Harvard-Thomdike Laboratory of Beth Israel Hospital, Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, MA 02215.
  • Harvey F. Lodish
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142

Abstract

<jats:p> 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 <jats:italic>myc</jats:italic> , <jats:italic>ras</jats:italic> , or <jats:italic>src</jats:italic> oncogenes were used. In <jats:italic>myc</jats:italic> -transfected cells, the rate of 2-deoxy-D-glucose uptake was unchanged. However, in cells transfected with activated <jats:italic>ras</jats:italic> and <jats:italic>src</jats:italic> oncogenes, the rate of glucose uptake was markedly increased. The increased transport rate in <jats:italic>ras</jats:italic> - and <jats:italic>src</jats:italic> -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- <jats:italic>O</jats:italic> -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 <jats:italic>ras</jats:italic> , <jats:italic>src</jats:italic> , and TPA, the predominant mechanism responsible for activation of the transport system is increased expression of the structural gene encoding the glucose transport protein. </jats:p>

Journal

  • Science

    Science 235 (4795), 1492-1495, 1987-03-20

    American Association for the Advancement of Science (AAAS)

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