1，25（OH）_2D_3及其类似物调节人原始巨核白血病细胞系增殖分化的机制  

Molecular mechanism of the effects of 1,25-dihydroxyvitamin D_3 and its novel analogues on proliferation and differentiation of a human megakaryoblastic leukemia cell line

作　　者：宋亮年[1] 郭嘉[1] 程涛[1] 

机构地区：[1]第二军医大学基础医学部病理生理学教研室,第二军医大学基础医学部分子遗传学教研室,第二军医大学长海医院血液内科

出　　处：《第二军医大学学报》1995年第6期507-512,共6页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金

摘　　要：１，２５（ＯＨ）_２Ｄ_３及其两种新型类似物（ＭＣ９０３和ＥＢ１０８９）对人原始巨核白血病细胞系ＨＩＭｅｇ的增殖分化过程有重要调节作用。本研究利用分子杂交及逆转录－聚合酶链反应首次证明，ＨＩＭｅｇ细胞中有１，２５（ＯＨ）_２Ｄ_３受体（ＶＤＲ）ｍＲＮＡ的表达，强烈提示１，２５（ＯＨ）_２Ｄ_３对ＨＩＭｅｇ细胞的作用是由ＶＤＲ介导的。同时还发现，１，２５（ＯＨ）_２Ｄ_３及其类似物、维甲酸在调节ＨＩＭｅｇ细胞增殖分化过程中，Ｃ－ｍｙｃｍＲＮＡ表达水平迅速降低，６ｈ时已基本达到最低水平，提示这些作用因子对ＨＩＭｅｇ细胞的抑制增殖和诱导分化作用是和Ｃ－ｍｙｃ癌基因的表达改变密切相关的。Our previous studies have revealed that 1,25-dihydroxyvitamin D_3[1,25 (OH)_2 D_3] and its two novel analogues (MC903 and EB1089) play an important role in the modulation of proliferation and differentiation of a newly established human megakaryoblastic leukemia cell line,HIMeg.However,the molecular mechanism of 1,25(OH)_2 D_3 action is still unknown.To this end,it is essential to ask if the high affinity nuclear receptor for 1,25 (OH)_2 D_3 (VDR) is expressed in HIMeg cells.In this study,the VDR mRNA expression was studied by molecular hybridization analysis and reverse-transcription-polymerase chain reaction (RT-PCR).It was demonstrated for the first time that specific VDR mRNA was expressed in HIMeg cells,strongly suggesting that the cellular effects of 1,25(OH)_2 D_3 and its analogues on HIMeg cells might be mediated by VDR.In the second part of this study,it was found that C-myc mRNA expression in HIMeg cells decreased rapidly in response to treatment with vitamin D_3 compounds or retinoic acid,reaching a maximum reduction 6 h following exposure and lasting for up to 24 h.These findings suggest that the induction of HIMeg cell growth suppression and cell differentiation induced by vitamin D_3 compounds and retinoic acid is closely related to the alteration in C-myc mRNA expression.

关 键 词：1 25(OH)2D3 白血病 巨核系 诱导分化 

分 类 号：R733.702[医药卫生—肿瘤]