ECTOPIC EXPRESSION OF THE ERYTHROPOIETIN RECEPTOR IN A MURINE INTERLEUKIN-6-DEPENDENT PLASMACYTOMA CELL-LINE (TEPC-2027) CONFERS PROLIFERATIVE RESPONSIVENESS TO ERYTHROPOIETIN

To compare the signal transduction pathways used by erythropoietin (Ep o) and interleukin-6 (IL-6), the cDNA for the murine Epo receptor (Epo -R) was introduced into an IL-6-responsive plasmacytoma cell line (TEP C-2027) by retrovirally mediated gene transfer, G418-resistant clones were amplified in IL-6 and studied for their ability to grow and diffe rentiate in response to Epo. Epo-R synthesized from the viral gene sho wed the same affinity for Epo as did the receptor on erythroid cells; however, the numbers of Epo receptors expressed on the cell membrane v aried among clones. After a delay of 3 to 5 days in the presence of Ep o, all the clones studied proliferated as well in response to Epo as i n response to IL-6, In response to IL-6, Stat3 was activated and JunB mRNA was accumulated, whereas in response to Epo, Jak2 and Stat5 were activated and JunB mRNA was not accumulated in Epo-R-expressing TEPC ( Epo-R/TEPC) cells. These results suggest that Epo and IL-6 transduced their proliferative signals through different pathways, Further studie s showed that, in Epo-R/TEPC cells, Epo neither induces the synthesis of erythroid-specific mRNA nor modifies the synthesis of gamma 1 Ig he avy chain, suggesting that ectopic expression of the Epo-R in plasmacy toma cells does not modify their differentiative potential. The data s how that Epo induces a proliferative response without differentiation providing a new cellular model for evaluating molecular events specifi c for proliferation. (C) 1997 by The American Society of Hematology.