Expression of transferrin receptors in human erythroleukemic lines: regulation in the plateau and exponential phase of growth.

The present study was undertaken in an attempt to elucidate the mechanism(s) underlying transferrin (TRF) receptor expression in human erythroleukemic (K562 and HEL) lines during the exponential and the plateau phase of growth. TRF receptor synthesis is enhanced when stationary cells are subcultured at low density in fresh medium. This rise occurs in either the presence or the absence of serum, which is associated with cell proliferation or quiescence, respectively. In the presence of serum, it is not inhibited by the addition of hydroxyurea (i.e., an agent blocking DNA synthesis). Thus, the receptor synthesis is enhanced not only in subcultures of actively proliferating cells (in the presence of serum), but also in subcultures of quiescent elements (in the absence of serum or upon the addition of serum plus hydroxyurea). Conversely, the ferritin content is markedly decreased when stationary cells are subcultured at low density, in either the presence or the absence of serum. These results suggest that stationary cells subcultured in fresh medium undergo a depletion of their intracellular iron pool, which in turn may represent the stimulus triggering TRF receptor synthesis. This hypothesis is supported by two observations: both the depletion of this pool and the rise in TRF receptor synthesis are more marked in the absence than in the presence of serum; addition of excess exogenous iron fully inhibits the rise of TRF receptor synthesis in cells subcultured with fresh medium and serum.