Down-regulation of c-myc and c-Ha-ras gene expression by tiazofurin in rat hepatoma cells.

E. Olah, Z. Kote, Y. Natsumeda, Y. Yamaji, G. Jarai, E. Lapis, I. Financsek, G. Weber

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Abstract

There was an overexpression of the c-myc gene (11-fold) and of the c-Ha-ras gene (2-fold) in rat hepatoma 3924A cells compared to normal rat liver as measured by dot-blot analysis of total cytoplasmic RNA. The overexpression of c-myc was attributed to a 10- to 14-fold amplification and rearrangement of the c-myc sequences as determined by Southern blot analysis. The expression of the c-myc also was dependent upon the proliferative state of the hepatoma cells. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide; NSC 286193), an inhibitor of the activity of IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of GTP biosynthesis, resulted in a rapid drop (less than 1 h) to 50% of control in the target enzyme activity in the hepatoma cells and in a subsequent marked decrease to 55% in GTP concentration. These events were followed at 12 h of tiazofurin treatment by a 3-fold reduction in the expression of the c-myc gene and a 9-fold decline in that of the c-Ha-ras gene. These results in the hepatoma cells provide evidence in support of the earlier demonstrated correlation in K562 cells between GTP concentration and expression of c-myc and c-ras genes (Olah et al., 1989). These genes might depend on GTP for their expression in hepatoma cells and they might cooperate in a signal pathway that controls cell proliferation.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalCancer biochemistry biophysics
Volume11
Issue number2
Publication statusPublished - Apr 1990

ASJC Scopus subject areas

  • Biophysics
  • Cancer Research

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    Olah, E., Kote, Z., Natsumeda, Y., Yamaji, Y., Jarai, G., Lapis, E., Financsek, I., & Weber, G. (1990). Down-regulation of c-myc and c-Ha-ras gene expression by tiazofurin in rat hepatoma cells. Cancer biochemistry biophysics, 11(2), 107-117.