Thrombopoietin induces histidine decarboxylase gene expression in c-mpl transfected UT7 cells.
The leukemic cell line UT7 is endowed with both megakaryocyte and basophil differentiation potential, as judged by its capacity to respond to PMA by displaying megakaryocytic and basophilic markers and to produce histamine by neosynthesis. Herein, we addressed the question whether the biological activities characteristic of basophil differentiation were still induced when c-mpl-transfected UT7 cells received a specific megakaryocytic differentiation signal delivered by thrombopoietin (TPO). Surprisingly, we found that histamine synthesis did effectively occur in response to the growth factor. This activity was not associated with megakaryopoiesis since it was not detected in megakaryocytes generated from CD34(+) cells cultured in the presence of TPO. Comparing different c-mpl-transfected cell lines, we found that the amount of histamine generated in response to TPO correlated with their responsiveness to PMA, but not with their level of c-mpl expression, thus revealing an intrinsic basophil differentiation potential. Both PMA- and TPO-induced histamine synthesis was reduced by PKC and MEKs inhibitors, indicating that the induction occurred through a common signalling pathway.
Pacilio
M
M
CNRS UMR 8603, Paris V University, Necker Hospital, Paris, France.
Debili
N
N
Arnould
A
A
Machavoine
F
F
Rolli-Derkinderen
M
M
Bodger
M
M
Arock
M
M
Duménil
D
D
Dy
M
M
Schneider
E
E
D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006632:Histamine / Q000096:biosynthesis; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D006632:Histamine; D013926:Thrombopoietin; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D006640:Histidine Decarboxylase; D013755:Tetradecanoylphorbol Acetate