HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line.
HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line.
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DOI：
10.1186/1475-2867-13-101
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发表时间：
2013-10-22
影响因子：
5.8
通讯作者：
Carè A
中科院分区：
文献类型：
--
作者：
Petrini M;Felicetti F;Bottero L;Errico MC;Morsilli O;Boe A;De Feo A;Carè A
同源异型盒(Homeobox，HOX)基因失控在很大程度上与人类白血病的发生有关。在HOXB簇中，HOXB1在一些分析的急性髓系白血病(AML)原代细胞和细胞系中不表达，而在正常终末分化的外周血细胞中表达。我们评价了HOXB1逆转录病毒转导人早幼粒细胞系HL60的生物学效应和转录组的变化。我们的结果表明，HOXB1的增强表达抑制了细胞的生长、增殖，诱导了单核细胞和粒细胞系的细胞凋亡和细胞分化。相应地，基因表达分析表明，HOXB1依赖于某些促癌基因的下调，同时伴随着凋亡和分化相关基因的上调，从而支持HOXB1在AML中的肿瘤抑制作用。最后，我们指出HOXB1启动子高甲基化是导致HOXB1沉默的一种机制。我们建议HOXB1作为具有肿瘤抑制特性的HOX家族的额外成员，这表明HOXB1/ATRA组合可能成为AML未来的治疗策略。
Homeobox (HOX) genes deregulation has been largely implicated in the development of human leukemia. Among the HOXB cluster, HOXB1 was silent in a number of analyzed acute myeloid leukemia (AML) primary cells and cell lines, whereas it was expressed in normal terminally differentiated peripheral blood cells. We evaluated the biological effects and the transcriptome changes determined by the retroviral transduction of HOXB1 in the human promyelocytic cell line HL60. Our results suggest that the enforced expression of HOXB1 reduces cell growth proliferation, inducing apoptosis and cell differentiation along the monocytic and granulocytic lineages. Accordingly, gene expression analysis showed the HOXB1-dependent down-regulation of some tumor promoting genes, paralleled by the up-regulation of apoptosis- and differentiation-related genes, thus supporting a tumor suppressor role for HOXB1 in AML. Finally, we indicated HOXB1 promoter hypermethylation as a mechanism responsible for HOXB1 silencing. We propose HOXB1 as an additional member of the HOX family with tumour suppressor properties suggesting a HOXB1/ATRA combination as a possible future therapeutic strategy in AML.
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影响因子：
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作者：
CELETTI, A;BARBA, P;MAGLI, MC
通讯作者：
MAGLI, MC
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56.9
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Lassus, P;Opitz-Araya, X;Lazebnik, Y
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Lazebnik, Y
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Asatiani, E;Huang, WX;Gelmann, EP
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作者：
Karpf, AR;Jones, DA
通讯作者：
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