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

Andrew K. Godwin, Michael W. Lieberman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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. The 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.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalMolecular Carcinogenesis
Volume4
Issue number4
DOIs
StatePublished - 1991

Keywords

  • Aphidicolin blocked
  • G/S synchronized
  • Gene expression
  • Hydroxyurea
  • Nocodazole
  • Rat-1 fibroblast

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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