Transformation by V-Erb-B - Induction of Apoptosis Is Abrogated in a Myeloid Cell-Line

Oncogene transformation represents a means to analyse events involved in myeloproliferation and leukemogenesis. We have previously shown that v-erb-B transforms a myeloid cell line (FDCP-1) to growth factor independence and acts to modulate the lineage of these cells allowing induction of erythroid differentiation. In this report we have compared apoptosis in parental and v-erb-B transformed FDCP-1 cells (FI v-erb-B). v-erb-B was found to protect these cells from apoptosis induced by IL-3 withdrawal, dexamethasone addition or serum withdrawal. In the case of IL-3 withdrawal, the suppression of apoptosis was reversed by herbimycin A, indicating that the effect was mediated through the tyrosine-kinase activity of the v-erb-B protein. The apoptotic protective effect exerted by v-erb-B for dexamethasone or serum withdrawal was seen despite growth suppression by these conditions. Taken together, these results indicate that transformation by this oncogene, in addition to its proliferation-enhancing properties, is due to its ability to inhibit apoptosis induced by growth factor withdrawal or growth suppression. The suppression of apoptosis induced by v-erb-B in hematopoietic cells appears to be important to the tumorigenic potential of this oncogene and may act as a means of in vivo tumor progression