Activation of apoptosis associated with enforced myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by interleukin-3 or erythropoietin.
The inappropriate expression of c-myc in cells deprived of growth factors has recently been implicated in the activation of programmed cell death (apoptosis). The studies described here examine the ability of interleukin-3 (IL-3) or erythropoietin (Epo) to suppress apoptosis that occurs in association with enforced myc expression during cell cycle arrest of a murine IL-3-dependent myeloid progenitor cell line, 32D. G1 arrest was observed when culturing 32D cells to high density in medium supplemented with IL-3, or at subconfluent densities in medium supplemented with Epo. Under both conditions, endogenous c-myc expression was downregulated and viability was maintained. In clones of cells in which c-myc is constitutively expressed from a retroviral vector, enforced c-myc expression was associated with the activation of apoptosis at high cell densities. Similarly, enforced c-myc expression was deleterious to cell survival when these cells were cultured in Epo, as apoptosis was evident within 6 hours. The results support the concept that inappropriate c-myc expression activates apoptosis and that neither IL-3 nor Epo can suppress this program under these conditions.
Askew
D S
DS
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105.
Ihle
J N
JN
Cleveland
J L
JL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection
D007377:Interleukin-3; D012333:RNA, Messenger; D004921:Erythropoietin; D004247:DNA