Signaling induced by erythropoietin and stem cell factor in UT-7/Epo cells: Transient versus sustained proliferation

UT-7/Epo cells are human factor-dependent erythroleukemic cells, requiring erythropoietin (Epo) for long-term growth. Stem cell factor (SCF) stimulate s proliferation of UT-7/Epo only transiently, for three to five days, An in vestigation of the signal transduction pathways activated by these cytokine s in UT-7/Epo cells may identify those signals specifically required for su stained growth. Proliferation assays demonstrate that SCF generates a subst antial growth th response in UT-7/Epo cells; however, the cells do not mult iply or survive past five to seven days, While Epo induces the activation o f JAK2 and STAT5, SCF stimulation shows no activation of JAK2 or STATs 1, 3 , or 5, The activation of MAPK (p42/44) by SCF was transient, lasting only 30 min, in contrast to Epo, which stimulated phosphorylation of p42/44 for up to 2 h, The expression of the early response genes c-fos, egr1, and cyto kine-inducible SH2 protein (CIS) in response to SCF or Epo stimulation demo nstrated that the transient expression of p42/44 correlated with the transi ent expression of c-fos and egr1, In addition, CIS was activated by Epo but not SCF, These data indicate that EpoR, JAK2, and STAT5 activation are not required for the initiation of proliferation of these erythroid cells, tha t the transient activation of p4U43 correlates with the transient gene expr ession of c-fos and egr1, and sustained expression of c-fos and egr1 as see n in UT-7/Epo cells continuously grown in Epo may be necessary for long-ter m proliferation.