Activation of the ribosomal DNA promoter in cells exposed to insulinlike growth factor I.

Abstract

We constructed a stable cell line, 3T3A5, which carried a chimeric gene in which the simian virus 40 T-antigen-coding gene was under the control of the mouse ribosomal DNA promoter. These cells expressed T antigen when they were growing exponentially in 10% fetal calf serum, but they all became T negative when incubated for 5 days in low-concentration serum. The readdition of serum or platelet-poor plasma again induced the expression of T antigen, which was accompanied by an increase in steady-state levels of the corresponding RNA. Among the various growth factors tested for their ability to induce T-antigen expression in 3T3A5 cells, only insulinlike growth factor I (IGF-I) could induce T antigen at physiological concentrations. The effect of IGF-I or platelet-poor plasma was abolished by an antibody to IGF-I. Other growth factors, like insulin and epidermal growth factor, could induce the expression of T antigen in 3T3A5 cells, but only at concentrations far above the physiological range. Other growth factors were totally ineffective. These results indicate that exposure of cells to IGF-I can activate transcription from the ribosomal DNA promoter.