Regulation of pim and myb mRNA accumulation by interleukin 2 and interleukin 3 in murine hematopoietic cell lines

Abstract

We have studied the mRNA accumulation of pim and myb genes in two interleukin 2- (IL2-)dependent, CTLL-2 and B6.1, and one IL3-dependent, FDC-P2, murine hematopoietic cell lines. To be able to dissociate the IL2 response from the phenomenon of lymphocyte activation, we used cell lines constitutively expressing the high affinity IL2 receptor. Deprivation of IL2 for 16 h led to an accumulation of CTLL-2 cells in G0/G1, and stimulation with IL2 induced a progression in S phase after 10 h. An increased accumulation of pim mRNA was observed in all cases in response to IL2 or IL3. This regulation did not require de novo protein synthesis and was, in CTLL-2 cells, mostly at the transcriptional level. Expression of myb was more complex: in CTLL-2 and FDC-P2 it is high and constitutive, while in B6.1 it is low and induced by IL2. This difference in myb regulation correlates with the higher level of myb expression in immature cells, as only B6.1 is functionally mature. Furthermore, it shows that transcription of myb does not affect the control of the cell cycle by the growth factors IL2 and IL3. These studies demonstrate that pim belongs to the small group of protooncogenes that can be induced during the primary response to growth factors (fos, myc, and myb) and that constitutive expression of myb, at least at the RNA level, is not sufficient to abrogate the growth factor requirement of hematopoietic cell lines.