Disregulation of Myc expression in murine bone marrow cells results in an inability to proliferate in sub-optimal growth factor and an increased sensitivity to DNA damage.
Derivatives of the murine bone marrow-derived, IL-3-dependent cell line, BAF3, were isolated following recombinant retroviral infection which showed disregulated expression of human c-Myc oncoprotein. Such cells entered apoptosis and lost viability more rapidly than parental BAF3 cells when IL-3 was removed. c-Myc disregulation also resulted in an inability of BAF3 cells to survive in either sub-optimal concentrations of IL-3, or saturating concentrations of IL-4 and insulin-like growth factor-1. Furthermore, BAF3 cells with disregulated c-Myc expression were more sensitive to the induction of apoptosis by DNA-damaging agents. These effects of c-Myc disregulation could be inhibited by co-expression of the Bcl-2 oncoprotein. The implications of these data for the transformation of haematopoietic cells by disregulation of Myc expression are discussed.
Malde
P
P
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Collins
M K
MK
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells; D002455:Cell Division / Q000235:genetics*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D014162:Transfection
D006133:Growth Substances; D007377:Interleukin-3; D016271:Proto-Oncogene Proteins c-myc; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I