Prothymosin α gene expression correlates with proliferation, not differentiation, of HL-60 cells

Abstract

Accumulating evidence suggests that prothymosin α has an as yet undefined intracellular, perhaps intranuclear, function related to cell proliferation. Prothymosin α mRNA and/or peptide levels increase when cells are stimulated to proliferate. Because proliferation and differentiation events are often inversely correlated, we examined prothymosin α gene expression during proliferation and differentiation of HL-60 myeloid leukemia cells. Steady-state levels of prothymosin α mRNA, which are high in exponentially growing HL-60, decrease within hours after induction of HL-60 to differentiate along the neutrophil pathway with dimethylsulfoxide (DMSO) or along the macrophage lineage with either tetradecanoylphorbol acetate (TPA) or bryostatin 1. The decline in prothymosin α mRNA in response to these differentiation signals parallels that of c-myc mRNA under the same conditions. We then determined whether the downregulation of prothymosin α and c-myc mRNA were due to differentiation or cessation or proliferation. Recombinant human γ-interferon induces monocytic differentiation of HL-60, but permits continued proliferation, and, under these conditions, expression of prothymosin α, as well as of c-myc, mRNA remains elevated. We conclude that prothymosin α and c-myc expression are coregulated in differentiating HL-60 and that their expression correlates with the proliferative state of HL-60 cells, rather than with the differentiated state. © 1993 by The American Society of Hematology.