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 mechanism.
The protooncogene c-myb is the cellular equivalent of the viral transforming oncogene v-myb. When human c-myb is constitutively 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 quasi-autocrine mechanism which modifies the growth factor requirements of the cell and its growth regulation.
Reiss
K
K
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541.
Ferber
A
A
Travali
S
S
Porcu
P
P
Phillips
P D
PD
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D015342:DNA Probes; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009857:Oncogenes; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin; D015183:Restriction Mapping; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D015342:DNA Probes; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D013937:Thymidine Kinase