Elevation of glucose transporter, c‐myc, and transin RNA levels by Ha‐rasT24 is independent of its effect on the cell cycle

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Abstract
Elevation of the steady‐state mRNA levels of glucose transporter and c‐myc are among the earliest changes in gene expression observed after Ha‐rasT24 stimulation of Rat‐1 fibroblasts to enter the cell cycle. Since the expression of these genes may be the result of either increased cell proliferation or a specific response to rasT24, we evaluated the expression of glucose transporter and c‐myc and their induction during the cell cycle in both parental Rat‐1 cells and cell lines bearing a metallothionein rasT24 fusion gene (MTrasT24). We showed that, although levels of glucose transporter and c‐myc mRNAs in Rat‐1 cells underwent a transient increase within hours of the addition of serum, epidermal growth factor, or 12‐O‐tetradecanoylphorbol‐13‐acetate to quiescent (G0) cells, the levels of glucose transporter and c‐myc mRNA otherwise remained constant throughout the normal cell cycle. In cells carrying MTrasT24 (MR5 cells), induction of rasT24 expression by ZnSO4 led to a rapid induction of glucose transporter and c‐myc mRNA expression in both quiescent (density‐arrested) and G1/S‐synchronized (aphidicolin‐blocked) cells. These increases exceeded the constitutive levels expressed in rapidly proliferating Rat‐1 cells, indicating that the ras oncogene has an effect on these genes that is independent of growth status. In addition, the transin gene, which is not expressed in proliferating Rat‐1 cells in the continuous presence of serum growth factors, was also induced after increased expression of the mutant ras gene. These results suggest that the induction of glucose transporter, c‐myc, and transin is the direct result of rasT24‐mediated alterations in cellular gene expression and is distinct from normal cell‐cycle events.