[The role of hydroxyurea in globin gene expression and cell differentiation of human erythroleukemia cell line].
The HEL cells, a human erythroleukemia cell line, express mainly the fetal globin gene and small amount of the embryonic (epsilon) globin gene, but not the adult (beta) globin gene. Hydroxyurea, a small organic compound, has been successfully used to treat sickle cell anemia and beta-thalessaemia. Our data demonstrated that the growth rate of HEL cell proliferation was inhibited by different doses of hydroxyurea (from 50 mumol/L to 200 mumol/L). Using both routine RT-PCR and quantitative PCR analyses, we revealed that the expression of beta-globin gene was sharply activated and alpha-globin gene was almost completely silenced when HEL cells were induced for 3 or 5 days. Meanwhile, gamma-globin gene was expressed with no much difference between induced and uninduced HEL cells. We also demonstrated that the expression of GATA-1 and NF-E 2, which were two of the most important transcription factors in erythrocyte development, was activated about 3 folds in the induced cells. We suggested that the induction of GATA-1 and NF-E 2 expression by hydroxyurea might lead to activation of the adult beta-globin gene through some pathways of signal transduction, therefore, hydroxyurea might play a role to induce HEL cells to terminal differentiation.
Gui
C Y
CY
Shanghai Institute of Cell Biology, Academia Sinica.
Jiang
C
C
Qian
R L
RL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D005914:Globins / Q000096:biosynthesis*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D014157:Transcription Factors; D005914:Globins; D006918:Hydroxyurea