Elevation of glucose transporter, c-myc, and transin RNA levels by Ha-rasT24 is independent of its effect on the cell cycle.
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.
Godwin
A K
AK
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Lieberman
M W
MW
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004261:DNA Replication; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D011905:Genes, ras; D007700:Kinetics; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D016196:S Phase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate