Ectopic expression of the erythropoietin receptor in a murine
interleukin-6-dependent plasmacytoma cell line (TEPC-2027) confers
proliferative responsiveness to erythropoietin
F Feger, A Dubart, C Lacout, I Dusanter-Fourt, P Mayeux, W Vainchenker and D Dumenil
INSERM U362, Institut Gustave Roussy, Villejuif, France.
To compare the signal transduction pathways used by erythropoietin (Epo)
and interleukin-6 (IL-6), the cDNA for the murine Epo receptor (Epo-R) was
introduced into an IL-6-responsive plasmacytoma cell line (TEPC-2027) by
retrovirally mediated gene transfer. G418-resistant clones were amplified
in IL-6 and studied for their ability to grow and differentiate in response
to Epo. Epo-R synthesized from the viral gene showed the same affinity for
Epo as did the receptor on erythroid cells; however, the numbers of Epo
receptors expressed on the cell membrane varied among clones. After a delay
of 3 to 5 days in the presence of Epo, all the clones studied proliferated
as well in response to Epo as in 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 studies showed that, in Epo-R/TEPC cells, Epo neither induces the
synthesis of erythroid-specific mRNA nor modifies the synthesis of gamma 1
lg heavy chain, suggesting that ectopic expression of the Epo-R in
plasmacytoma cells does not modify their differentiative potential. The
data show that Epo induces a proliferative response without differentiation
providing a new cellular model for evaluating molecular events specific for
proliferation.
Volume 89,
Issue 2,
pp. 435-445,
01/15/1997
Copyright © 1997 by The American Society of Hematology
