The insulin-like growth factor 1 receptor is required for the proliferation of hemopoietic cells.
We have investigated the role of the insulin-like growth factor one (IGF1) receptor and its relationship to the proto-oncogene c-myb in the growth of two types of hemopoietic cells: mitogen-stimulated human peripheral blood mononuclear cells and a human promyelocytic cell line (HL-60). Using the antisense strategy and the reverse transcriptase polymerase chain reaction (RT-PCR), we show that expression of the IGF1 receptor is required for the entry into S phase of both stimulated lymphocytes and HL-60 cells. The inhibition of DNA synthesis by antisense oligomers to the IGF1 receptor RNA is accompanied by an inhibition of the expression of the mRNA for a DNA synthesis gene, proliferating cell nuclear antigen (PCNA), the co-factor of DNA polymerase delta. Inhibition of c-myb expression results in a decrease in IGF1 receptor mRNA levels; on the other hand, inhibition of IGF1 receptor expression has no effect on c-myb mRNA levels. A tentative temporal relationship between these three genes (c-myb, IGF1 receptor, PCNA) is proposed.
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541.
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K
Reiss
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Porcu
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Sell
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Pietrzkowski
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R
Baserga
D001483:Base Sequence; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009857:Oncogenes; D018809:Proliferating Cell Nuclear Antigen; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D004247:DNA; D017526:Receptor, IGF Type 1; D013755:Tetradecanoylphorbol Acetate