v-myb blocks granulocyte colony-stimulating factor-induced myeloid cell differentiation but not proliferation.
To understand the effects of v-myb expression on mammalian hematopoietic cell differentiation, we have constructed a retroviral vector which can efficiently express v-myb gene product in mammalian cells. Infection of interleukin-3-dependent murine progenitor cell line 32D Cl3, which undergoes terminal differentiation to mature granulocytes in the presence of granulocyte colony-stimulating factor (GCSF), with this recombinant retrovirus does not abrogate its requirement of interleukin-3 for growth. However, expression of v-myb in these cells blocks their ability to differentiate in response to GCSF. Instead, the v-myb-infected cells proliferate indefinitely in the presence of GCSF. 32D Cl3 cells infected with empty vector carrying only the neomycin resistance gene responded to the addition of GCSF in a manner identical to that of the uninfected cells and underwent terminal differentiation into granulocytes. These results suggest that oncogenic forms of myb gene bring about transformation by blocking the differentiation signal derived by cytokines while promoting the proliferative signal transduction pathways.
Patel
G
G
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Kreider
B
B
Rovera
G
G
Reddy
E P
EP
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D007781:Lactoferrin / Q000235:genetics; D051379:Mice; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D009195:Peroxidase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000494:pharmacology*
D007377:Interleukin-3; D020626:Oncogene Proteins v-myb; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase; D007781:Lactoferrin