A differential screen for ligand-regulated genes:: Identification of HoxA10 as a target of vitamin D3 induction in myeloid leukemic cells

被引:61
作者
Rots, NY [1 ]
Liu, M [1 ]
Anderson, EC [1 ]
Freedman, LP [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA
关键词
D O I
10.1128/MCB.18.4.1911
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
1,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3], the hormonal ligand for vitamin D-3, is a potent inducer of myeloid-leukemic-cell differentiation. Such cells differentiate exclusively into monocytes/macrophages in response to this ligand, Since 1,25(OH)(2)D-3 transduces its hormone signal through the vitamin D, receptor (VDR), a ligand modulated transcription factor and member of the nuclear hormone receptor superfamily, we sought to identify direct VDR target genes induced during this differentiation process, To do so, we applied a modified differential screen with a nascent-RNA purification strategy using biases for immediate-early-response genes induced by 1,25(OH)(2)D-3 in the myelomonocytic cell line U937, Using this screen, we had previously identified p21(Waf1/Cip1) as a gene transcriptionally induced by 1,25(OH)(2)D-3 and demonstrated that this induction facilitates the differentiation of U937 cells into monocytes/macrophages (24). Here, we describe in detail our differential screen strategy and the identification and isolation of 20 1,25(OH)(2)D-3-inducible genes or unknown cDNAs by means of this screen, One gene newly identified as a target of VDR regulation in myeloid cells is the homeobox HoxA10 gene, HoxA10 protein may act as a general regulator of cell growth, since overexpression of HoxA10 facilitated the differentiation of U937 cells into monocytes/macrophages independent of 1,25(OH)(2)D-3 and acted to strongly inhibit the growth of the breast cancer cell line MCF-7 by arresting these cells in G(1).
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页码:1911 / 1918
页数:8
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