p~(53)基因在U 937细胞生长和分化过程中的调节作用

本文报道了p~(53)基因对人白血病细胞系U 937细胞生长和分化的调节作用。重组人GM-CSF(rhGM-CSF)可诱导U 937细胞向成熟巨噬细胞分化,这反映在分化后的细胞表达有巨噬细胞许多表型特征和功能活性。在这一分化过程中同时伴随着p~(53)基因的表达增加和U 937细胞生长受抑。进一步,用反义脱氧寡聚核苷酸抑制试验特异性地抑制p~(53)基因表达,结果发现p~(53)反义脱氧寡聚核苷酸可以明显抑制rhGM-CSF诱导U 937细胞向成熟巨噬细胞分化,同时也明显解除rhGM-CSF介导细胞分化过程中的细胞生长抑制作用。这些结果说明p~(53)基因在U 937细胞的生长和分化过程中可能起偶联调控作用。

THE ROLE OF p~(53) GENE IN THE SWITCH OF U 937 LEUKEMIC CELLS FROM GROWTH INTO DIFFERENTIATION

The expression of p~(53) gene has been found to be regulated during the induction of differentiation of U 937 leukemic cells into mature macrophages by recombinant human granulocyte- macrophage colony stimulating factors (rhGM-CSF) We showed here that the increased expression of p~(53) seemed to be necessary for the differentiation of U 937 cells induced by rhGM-CSF. The inhibition of p~(53) expression by a p~(53) 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 p~(53) sense oligodeoxynucleotide had no any effect. Furthermore, we have analysed the growth of U 937 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 inhibiton of p~(53) expression partially diminished the growth-inhibitory effect of rhGM-CSF on U 937 cells, These results suggested that the p~(53) 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 p~(53) induced by rhGM-CSF may be a coupling event of switch of U 937 cells from growth into differentiation.