The Protooncogene c-myb Increases the Expression of Insulin-like Growth Factor 1 and Insulin-like Growth Factor 1 Receptor Messenger RNAs by a Transcriptional Mechanism1

The protooncogene c-myb is the cellular equivalent of the viral trans forming oncogene \-myh. When human c-myb is constitutive!}expressed in Balb/c3T3 cells it abrogates their absolute requirement for insulin-like growth factor 1 (IGF-1). We show now, in two different cell lines, that the constitutive expression of the protooncogene c-myb causes an increase in both IGF-1 and IGF = 1 receptor mRNA levels. This increase in mRNA levels is due, at least in part, to an increase in the rate of transcription since, by run-on assay, cells carrying the human c-myb cDNA show a 3-fold increase in transcriptional rates in comparison to the control parent cell lines. The increased expression of IGF-1 receptor mRNA also results in an increased number of IGF-1 binding sites per cell. Although some oncogenes have been described that are homologous to growth factors, or growth factor receptors, c-myb seems to represent a novel way of oncogene action inasmuch as it increases the expression of both a growth factor receptor and its ligand, thus establishing a quasiautocrine mechanism which modifies the growth factor requirements of the cell and its growth regulation.