Ectopic expression of the erythropoietin receptor in a murine interleukin-6-dependent plasmacytoma cell line (TEPC-2027) confers proliferative responsiveness to erythropoietin

• Published in: Blood Vol. 89; no. 2; pp. 435 - 445
• Main Authors: FEGER, F, DUBART, A, LACOUT, C, DUSANTER-FOURT, I, MAYEUX, P, VAINCHENKER, W, DUMENIL, D
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.01.1997
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Cell physiology; Erythropoietin - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic - drug effects; Gene Transfer Techniques; Humans; Interleukin-6 - pharmacology; Mice; Molecular and cellular biology; Plasmacytoma - genetics; Plasmacytoma - metabolism; Plasmacytoma - pathology; Receptors, Erythropoietin - genetics; Signal transduction; Signal Transduction - drug effects; Tumor Cells, Cultured; Cell proliferation; Lymphoid cell; Erythropoietin; Cytokine; Rodentia; Glycoprotein hormone; In vitro; Interleukin 6; Signal transduction; Vertebrata; Mammalia; Transfection; Complementary DNA; Mouse; Animal; Established cell line; Plasmacytoma; Differentiation; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v89.2.435

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.