ACTIVATION OF 4 HOMEOBOX GENE CLUSTERS IN HUMAN EMBRYONAL CARCINOMA-CELLS INDUCED TO DIFFERENTIATE BY RETINOIC ACID
ACTIVATION OF 4 HOMEOBOX GENE CLUSTERS IN HUMAN EMBRYONAL CARCINOMA-CELLS INDUCED TO DIFFERENTIATE BY RETINOIC ACID
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DOI：
10.1111/j.1432-0436.1988.tb00798.x
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发表时间：
1988-01-01
期刊：
影响因子：
2.9
通讯作者：
ANDREWS, PW
中科院分区：
文献类型：
--
作者：
MAVILIO, F;SIMEONE, A;ANDREWS, PW
我们研究了来自Hox 1、Hox 2、Hox 3和Hox 5群的9个同源盒基因在人胚胎癌（EC）细胞系中作为干细胞和暴露于分化诱导剂维甲酸（RA）、六亚甲基双乙酰胺（HMBA）和溴脱氧尿苷（BUdR）后的表达。同源盒基因在干细胞中没有表达，而在多能EC细胞系NTERA-2，克隆D1 （NT2/D1）的培养中，在RA诱导的分化后，所有基因都被激活，尽管具有不同的动力学。在将RA从培养基中去除几周后，至少有一些同源盒基因在分化细胞中稳定表达。然而，初始暴露于RA的时间长度是实现稳定基因表达的关键因素，并且在不同的基因组之间是不同的，至少在一种情况下，在来自同一基因的不同转录本之间也是不同的。与HMBA或BUdR诱导分化的NT2/D1细胞未检测到同源盒基因表达。同样，在裸鼠体内由NT2/D1细胞产生的异种移植物肿瘤中未检测到表达，尽管这种类型的肿瘤含有大部分分化细胞。其他测试的人EC系，即833KE、2102Ep或1156QE，对RA没有反应，也没有表达同源盒基因。异种移植瘤中未检测到833KE和2102Ep的表达，主要含有EC细胞。这些数据表明，同源盒基因的激活特异性伴随着ra诱导的NT2/D1细胞分化，从而为研究同源盒基因调控的分子基础以及同源盒在细胞分化中的可能作用提供了一个很好的模型。
We have studied the expression of nine homeobox genes from Hox 1, Hox 2, Hox 3 and Hox 5 clusters in human embryonal carcinoma (EC) cell lines analyzed as both stem cells and after exposure to the differentiation-inducing agents retinoic acid (RA), hexamethylenebisacetamide (HMBA) and bromodeoxyuridine (BUdR). None of the homeobox genes was expressed in stem cells, whereas all were activated, although with different kinetics, in cultures of the pluripotent EC cell line NTERA-2, clone D1 (NT2/D1), following differentiation induced by RA. At least some homeobox genes were stably expressed in differentiated cells several weeks after removal of RA from the culture medium. However, the length of initial exposure to RA is a critical factor in achieving stable gene expression, and differs among the different sets of genes and, at least in one case, among different transcripts from the same gene. No homeobox gene expression was detected in NT2/D1 cells induced to differentiate with HMBA or BUdR. Also, no expression was detectable in xenograft tumors generated by NT2/D1 cells in nude mice, even though tumors of this type contain mostly differentiated cells. Other human EC lines tested, i.e., 833KE, 2102Ep or 1156QE, did not differentiate in response to RA and did not express homeobox genes. No expression was detectable in xenograft tumors of 833KE and 2102Ep, containing essentially EC cells. These data indicate that homeobox-gene activation specifically accompanies RA-induced differentiation of NT2/D1 cells, thereby providing an excellent model for studying the molecular basis of homeobox-gene regulation and the possible role of the homeobox in cell differentiation.