Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation
Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation
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DOI：
10.1159/000217965
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Cohn, SL
中科院分区：
文献类型：
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作者：
Manohar, CF;Salwen, HR;Cohn, SL
神经母细胞瘤（NB）是一种源自胚胎神经嵴组织的肿瘤，其发病机制的早期事件似乎是神经母细胞分化受阻。然而，NE细胞可以在体外被多种化学物质诱导分化，包括维甲酸（RA）和二丁基环AMP （db-cAMP）。同源盒（HOX）基因编码的一个转录因子家族在果蝇、爪蟾和哺乳动物的胚胎分化和发育中起着至关重要的作用。我们之前已经通过基于敏感pcr的方法，从诱导与RA分化的人LA-N-5 NE细胞系中制备的cDNA文库中鉴定了6个HOX基因（HOXC6, HOXC8, HOXD1, HOXD4， HOXD8和HOXD9）。在本报告中，我们研究了这6个HOX基因在一系列化学诱导分化的NE细胞系中的调控作用。未经处理的NE细胞表达低水平或无法检测到HOX mRNA，并且在诱导细胞中仍无法检测到HOXC8。然而，在ra处理的NE细胞系中，HOXC6、HOXD1和HOXD8的表达被显著诱导，尽管上调的模式和程度不同。db-cAMP处理还能诱导HOXC6和HOXD8在三种NE细胞系中的两种表达。在两个和一个ra处理的NE细胞系中分别观察到低水平的HOXD4和HOXD9诱导。在化学诱导分化的人NE细胞中，HOXC6、HOXD1和HOXD8的表达上调似乎与向分化神经元表型的成熟有关。
An early event in the pathogenesis of neuroblastoma (NB), a tumor derived from embryonal neural crest tissue, appears to be the arrested differentiation of neuroblasts. However, NE cells can be induced to differentiate in vitro with numerous chemicals including retinoic acid (RA) and dibutyryl cyclic AMP (db-cAMP). One family of transcription factors, encoded by the homeobox (HOX) genes, plays a crucial role in Drosophila, Xenopus, and mammalian embryonic differentiation and development. We have previously identified six HOX genes (HOXC6, HOXC8, HOXD1, HOXD4, HOXD8, and HOXD9), by a sensitive PCR-based approach, in a cDNA library prepared from the human LA-N-5 NE cell line induced to differentiate with RA. In this report, we studied the regulation of these six HOX genes in a series of NE cell lines chemically induced to differentiate. Untreated NE cells express low or undetectable levels of HOX mRNA, and HOXC8 remains undetectable in the induced cells. However, a significant induction of HOXC6, HOXD1, and HOXD8 expression is seen in the RA-treated NE cell lines, albeit with different patterns and degree of up-regulation. db-cAMP treatment also induced HOXC6 and HOXD8 expression in two of the three NE cell lines analyzed. Low levels of HOXD4 and HOXD9 induction were observed in two and one RA-treated NE cell line, respectively. Up-regulation of HOXC6, HOXD1, and HOXD8 expression in human NE cells, chemically induced to differentiate, appears to be associated with maturation toward a differentiated neuronal phenotype.