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 (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.
Féger
F
F
INSERM U362, Institut Gustave Roussy, Villejuif, France.
Dubart
A
A
Lacout
C
C
Dusanter-Fourt
I
I
Mayeux
P
P
Vainchenker
W
W
Duménil
D
D
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018014:Gene Transfer Techniques; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D010954:Plasmacytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017467:Receptors, Erythropoietin / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D017467:Receptors, Erythropoietin; D004921:Erythropoietin