Activation of cMGF expression is a critical step in avian myeloid leukemogenesis.
A non-leukemogenic version of the v-myb oncogene causes in vitro transformation of avian myeloblasts, which are dependent on chicken myelomonocytic growth factor (cMGF). We have shown that this version of v-myb, when combined with the erythroleukemia-inducing v-erbB oncogene, is capable of causing a mixed myeloid and erythroid leukemia. Myeloid leukemic cells transformed by this construct produce cMGF. To test whether autocrine growth stimulation via cMGF is the essential contribution of the tyrosine kinase oncogene v-erbB in avian myeloid leukemogenesis we constructed another retrovirus containing both the non-leukemogenic v-myb and the cMGF cDNA. This virus induced myeloid leukemia at high efficiency. In a third construct we combined v-myb with the human EGF-receptor gene. Myeloid cells transformed by this construct could be stimulated to grow by the addition of cMGF or EGF. Growth stimulation with EGF was blocked by a cMGF antiserum indicating that activation of a normal tyrosine kinase-type receptor induces cMGF expression but does not bypass the cMGF requirement. We conclude that cMGF plays a key role in the growth regulation of normal and transformed avian myeloid cells.
Metz
T
T
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, FRG.
Graf
T
T
Leutz
A
A
D000818:Animals; D030161:Avian Proteins; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D002645:Chickens; D016207:Cytokines; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D007942:Leukemia, Experimental / Q000473:pathology; D018739:Oncogene Proteins v-erbB; D020626:Oncogene Proteins v-myb; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D014162:Transfection
D030161:Avian Proteins; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C059626:MGF protein, chicken; D018739:Oncogene Proteins v-erbB; D020626:Oncogene Proteins v-myb; D009856:Oncogene Proteins, Viral; D015682:Retroviridae Proteins, Oncogenic; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases