THE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR IS REQUIRED FOR THE PROLIFERATION OF HEMATOPOIETIC-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.