B-Myb prevents growth arrest associated with terminal differentiation of monocytic cells - PubMed (original) (raw)
. 1996 Jan 18;12(2):355-63.
Affiliations
- PMID: 8570212
B-Myb prevents growth arrest associated with terminal differentiation of monocytic cells
J Bies et al. Oncogene. 1996.
Abstract
B-Myb is a transcriptional regulator of gene expression and is highly homologous to c-Myb in its N-terminal DNA binding domain. However, unlike c-myb, whose expression is restricted largely to immature hematopoietic cells, B-myb mRNA has been found to be expressed in all proliferating mammalian cell lines and is clearly regulated in a cell cycle dependent manner. That c-Myb and B-Myb proteins perform different roles in proliferation and/or differentiation is suggested by the redundancy of their expression. It was previously shown that degenerated c-Myb expression can inhibit IL-6 induced terminal differentiation of the leukemia cell line M1. We found that, unlike the downregulation of c-Myb protein which is an early response of progenitor M1 cells to IL-6 treatment, the downregulation of B-Myb occurs late, just prior to terminal differentiation and growth arrest. It was, therefore, of interest to examine the role of the murine B-Myb protein in the proliferation and differentiation of the M1 cells and to compare these effects to those of c-Myb in the same system. Clones ectopically producing B-Myb, like those ectopically expressing c-Myb, proliferated in the presence of the differentiation-inducing agent and did not undergo the programmed cell death which normally follows terminal macrophage differentiation. In addition, the cell-cycle distribution of M1/B-Myb cells was comparable to untreated cells. Although M1/B-Myb and M1/c-Myb clones treated with IL-6 appeared quite immature, differentiation markers were demonstrated to be maintained at near normal levels (e.g. MyD88, Mac-2), or be partially reduced in expression (C3, Fc and Mac-1 receptors) suggesting that the cells had undergone commitment to maturation, but were unable to terminally differentiate.
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