[The role of p53 gene in the switch of U937 leukemic cells from growth into differentiation].
The expression of p53 gene has been found to be regulated during the induction of differentiation of U937 leukemic cells into mature macrophages by recombinant human granulocyte- macrophage colony stimulating factors (rhGM-CSF) We showed here that the increased expression of p53 seemed to be necessary for the differentiation of U937 cells induced by rh-GM-CSF. The inhibition of p53 expression by a p53 antisense oligodeoxynucleotide lead to the significant decrease of formation of mature macrophages from U 937 cells in the presence of rhGM-CSF. By contrast, the p53 sense oligodeoxynucleotide had no any effect. Furthermore, we have analysed the growth of U937 cells in the presence or absence of rhGM-CSF. The results showed that rhGM-CSF dramatically inhibited the growth of U 937 cells in the cultures. At the same time, the antisense inhibition experiment demonstrated that the inhibition of p53 expression partially diminished the growth-inhibitory effect of rhGM-CSF on U 937 cells. These results suggested that the p53 was required for the initiation of rhGM-CSF-induced differentiation of U 937 cells on one hand, and the inhibition of cell growth on the other hand. Thus we deduce that the increased expression of p53 induced by rhGM-CSF may be a coupling event of switch of U 937 cells from growth into differentiation.
Wu
J
J
Department of Biochemistry, Nanjing University.
Wang
M L
ML
Sheng
Y
Y
Zhu
D X
DX
D002454:Cell Differentiation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D016178:Granulocyte-Macrophage Colony-Stimulating Factor