Manohar C F, Furtado M R, Salwen H R, Cohn S L
Department of Pediatrics, Northwestern University, Chicago IL 60611.
Biochem Mol Biol Int. 1993 Jul;30(4):733-41.
Neuroblastoma, a malignancy of early childhood arises in the embryonal neural crest. Neuroblastoma cells are in a state of arrested differentiation; however, they can be induced to differentiate in vitro by retinoic acid. As a first step toward understanding the molecular mechanisms of neuroblastoma differentiation we analyzed the expression pattern of the developmentally important Homeobox genes in cells treated with retinoic acid. The strategy employed involved rapid screening of a cDNA library prepared from retinoic acid treated human LA-N-5 neuroblastoma cells for Homeobox genes by the polymerase chain reaction. Multiple Homeobox genes were amplified from recombinant phage DNA using degenerate primers directed against the conserved homeobox. To date 6 Homeobox genes (HoxC6, HoxC8, HoxD1, HoxD4, HoxD8, and HoxD9) have been identified in the cDNA library prepared from LA-N-5 cells treated with retinoic acid. HoxD1 and HoxC8 are being reported for the first time to be expressed in neuroblastoma cells. Preliminary studies indicate that there is an induction of Homeobox gene expression in differentiating LA-N-5 neuroblastoma cells.
神经母细胞瘤是一种发生于胚胎神经嵴的儿童早期恶性肿瘤。神经母细胞瘤细胞处于分化停滞状态;然而,它们可在体外被视黄酸诱导分化。作为理解神经母细胞瘤分化分子机制的第一步,我们分析了经视黄酸处理的细胞中对发育至关重要的同源框基因的表达模式。所采用的策略包括通过聚合酶链反应快速筛选从经视黄酸处理的人LA-N-5神经母细胞瘤细胞制备的cDNA文库以寻找同源框基因。使用针对保守同源框的简并引物从重组噬菌体DNA中扩增出多个同源框基因。迄今为止,在从经视黄酸处理的LA-N-5细胞制备的cDNA文库中已鉴定出6个同源框基因(HoxC6、HoxC8、HoxD1、HoxD4、HoxD8和HoxD9)。HoxD1和HoxC8首次被报道在神经母细胞瘤细胞中表达。初步研究表明,在分化的LA-N-5神经母细胞瘤细胞中存在同源框基因表达的诱导。