TY - JOUR
T1 - The inhibitory effect of the proinflammatory cytokine TNFα on erythroid differentiation involves erythroid transcription factor modulation
AU - Buck, Isabelle
AU - Morceau, Franck
AU - Cristofanon, Silvia
AU - Reuter, Simone
AU - Dicato, Mario
AU - Diederich, Marc
PY - 2009
Y1 - 2009
N2 - The hematopoietic transcription factor GATA-1 regulates the expression of several genes associated with differentiation of erythroid cells. We show here the inhibitory effect of tumor necrosis factor α (TNFα), a proinflammatory cytokine, on hemoglobinization and erythroid transcription factor GATA-1 expression in erythroleukemia (HEL) as well as in chronic myelogenous leukemia (K562) cells, which were induced to differentiate towards the erythroid lineage after aclacinomycin (Acla), doxorubicin (Dox) or hemin (HM) treatment. As a result, we observed i) a decreased expression of Friend of GATA-1 (FOG-1), an essential cofactor of GATA-1 transcription factor, ii) a downregulation of GATA-1 by proteasomal degradation and iii) a reduced acetylation level of GATA-1 in HM-induced K562 cells after TNF treatment. As a result, these modifications i) decreased the level of GATA-1/FOG-1 complex, ii) unsettled the GATA-1/GATA-2 balance, iii) reduced GATA-1 transcriptional activity and iv) inhibited erythroid marker gene expression (glycophorin A, erythropoietin receptor, γ-globin) independently of the cell line or the inducer used. These data provided new insights into the role of GATA-1 regulation in TNFα-mediated inhibition of erythroid differentiation in erythroleukemia.
AB - The hematopoietic transcription factor GATA-1 regulates the expression of several genes associated with differentiation of erythroid cells. We show here the inhibitory effect of tumor necrosis factor α (TNFα), a proinflammatory cytokine, on hemoglobinization and erythroid transcription factor GATA-1 expression in erythroleukemia (HEL) as well as in chronic myelogenous leukemia (K562) cells, which were induced to differentiate towards the erythroid lineage after aclacinomycin (Acla), doxorubicin (Dox) or hemin (HM) treatment. As a result, we observed i) a decreased expression of Friend of GATA-1 (FOG-1), an essential cofactor of GATA-1 transcription factor, ii) a downregulation of GATA-1 by proteasomal degradation and iii) a reduced acetylation level of GATA-1 in HM-induced K562 cells after TNF treatment. As a result, these modifications i) decreased the level of GATA-1/FOG-1 complex, ii) unsettled the GATA-1/GATA-2 balance, iii) reduced GATA-1 transcriptional activity and iv) inhibited erythroid marker gene expression (glycophorin A, erythropoietin receptor, γ-globin) independently of the cell line or the inducer used. These data provided new insights into the role of GATA-1 regulation in TNFα-mediated inhibition of erythroid differentiation in erythroleukemia.
KW - Anemia
KW - Cancer
KW - Friend of GATA-1
KW - GATA-1/-2
KW - Inflammation
KW - Tumor necrosis factor α
UR - http://www.scopus.com/inward/record.url?scp=64049095648&partnerID=8YFLogxK
U2 - 10.3892/ijo_00000212
DO - 10.3892/ijo_00000212
M3 - Article
C2 - 19212691
AN - SCOPUS:64049095648
SN - 1019-6439
VL - 34
SP - 853
EP - 860
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 3
ER -