DECREASED EXPRESSION OF N-MYC PRECEDES RETINOIC ACID-INDUCED MORPHOLOGICAL-DIFFERENTIATION OF HUMAN NEURO-BLASTOMA

DECREASED EXPRESSION OF N-MYC PRECEDES RETINOIC ACID-INDUCED MORPHOLOGICAL-DIFFERENTIATION OF HUMAN NEURO-BLASTOMA
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DOI:
10.1038/313404a0
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发表时间:
1985-01-01
期刊:
影响因子:
64.8
通讯作者:
ISRAEL, MA
ISRAEL, MA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
THIELE, CJ;REYNOLDS, CP;ISRAEL, MA

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原癌基因可能在对正常细胞的生长和分化至关重要的细胞过程中很重要1,2。N-mycis是一种与原癌基因c-mycand具有有限同源性的DNA序列,已发现其在神经母细胞瘤(一种神经外胚层起源的儿童肿瘤)的原代组织3和细胞系4,26中扩增。这种胚胎性肿瘤的分化具有临床重要性,因为已经注意到偶尔的肿瘤可以在体内分化为良性神经节细胞瘤5,7,28。在体外,许多人神经母细胞瘤细胞系可以被各种试剂诱导分化为形态学和生物化学6 -11。维甲酸(RA),维生素A的类似物,已被证明可以抑制神经母细胞瘤细胞生长和软琼脂中的克隆能力,并诱导广泛的神经突生长8,9。因此,我们研究了N-myc表达与这些细胞体外分化的关系。我们在这里报告,在RA诱导分化的情况下,检测到6小时内的治疗和细胞周期的变化和形态分化之前的表达水平下降。
Proto-oncogenes may be important in the cellular processes central for the growth and differentiation of normal cells1,2. N-mycis a DNA sequence which shares limited homology to the protooncogene c-mycand has been found to be amplified in both primary tissue3and cell lines from neuroblastoma4,26, a childhood tumour of neuroectodermal origin. Differentiation of this embryonal tumour is of clinical importance, since occasional tumours have been noted to differentiatein vivoto benign ganglioneuroma5,7,28.In vitro, many human neuroblastoma cell lines can be induced to differentiate morphologically and biochemically by a variety of agents6–11. Retinoic acid (RA), an analogue of vitamin A, has been shown to inhibit neuroblastoma cell growth and clonability in soft agar, and to induce extensive neurite outgrowth8,9. Therefore we examined the relationship of N-mycexpression to thein vitrodifferentiation of these cells. We report here that in the case of RA-induced differentiation, a decreased level of expression is detected within 6 h of treatment and precedes both cell-cycle changes and morphological differentiation.