β1,3-N-乙酰氨基葡萄糖转移酶-2,-8(β3GnT-2,β3GnT-8)共同参与多聚N-乙酰氨基乳糖([Galβ1→4GlcNAcβ1→3]n)的合成,从而使得细胞表面的相应糖链结构延长进而影响细胞的恶性转化.已有研究表明,在全反式维甲酸诱导人白血病细胞株HL-60分化过程中β3GnT-2,-8的表达上调,但其分子机制不明.本文旨在探讨ATRA诱导HL-60分化过程中,转录因子Ets-1对β3GnT-2,-8表达调控的分子机制.采用10-6mol/L ATRA诱导人白血病细胞株HL-60向粒系分化,RT-PCR检测到细胞中Ets-1的表达明显增加;进一步采用染色质免疫沉淀(ChIP)结合电泳迁移率变动实验(EMSA)检测证实,有活化的Ets-1结合至β3GnT-2/-8基因调控区.以上结果表明,转录因子Ets-1对人白血病细胞株HL-60分化过程中β3GnT-2,-8基因有表达调控作用.
The expression of β1,3-N-acetyl glucosamonyltransferase-2 and-8(β3GnT-2,β3GnT-8) genes,which involved in the biosynthesis of poly-N-acetyllactosamine(polyLacNAc) of cancer cells,was increased and associated with the malignant transformation.We have previously shown that the human β3GnT-2 and-8 genes were up-regulated during all-trans-retinoid acid(ATRA)-induced differentiation of human acute myeloid leukemia HL-60 cells.Here we investigated the mechanism of β3GnT-2 and-8 genes activation by the transcription factor Ets-1.RT-PCR analysis showed a significant increase of Ets-1 expression during ATRA-induced differentiation in HL-60 cells.Chromatin immuno-precipitation(ChIP) and electrophoretic mobility shift assay(EMSA) revealed Ets-1 to regulate β3GnT-2 and-8 transcription in vivo and in vitro.The results indicates that Ets-1 played an essential role in the transcriptional activation of the β3GnT-2 and β3GnT-8 genes.