ENFORCED EXPRESSION OF FULL-LENGTH C-MYB LEADS TO DENSITY-DEPENDENT TRANSFORMATION OF MURINE HEMATOPOIETIC-CELLS

The oncogenic activation of c-myb has been associated with structural alterations to the Myb protein. Although such alterations can increase the ability of Myb to transform haemopoietic cells, it has been unres olved whether over-expression of wild type (WT) c-Myb can lead to tran sformation. We show here that infection with a retrovirus that express es WT i.e. full length c-Myb leads to transformation of primary haemop oietic cells (as indicated by clonogenic assays). The transformed cell s are similar to those obtained with carboxyl-truncated (CT) c-Myb in that they show phenotypic and morphological characteristics of early m yeloid cells and remain dependent on exogenous growth factors. Cells e xpressing WTMyb form lower numbers of colonies on average and have a g reater tendency to spontaneously differentiate than those expressing t runcated c-Myb. Additionally, our results show that transformation by both forms of Myb is dependent on the density at which the infected ce lls are cultured, and that low levels of transformation can be increas ed by addition of conditioned medium from myb transformed cells grown at high density. This implies that transformation can be enhanced by t he effects of an autocrine growth factor. Moreover, the production of, or sensitivity to, such a factor may be influenced by Myb itself, sin ce CT Myb-infected cells cultured at low densities show higher levels of transformation than WT Myb-infected cells.