Gene Expression Profiles of Differentiating laukemia cells.

目的：白血病和神经母细胞瘤（NB）是主要的儿童实体肿瘤，预后较差。已知维生素D3可诱导HL60白血病细胞系分化。已知13-顺式维甲酸不仅在体外诱导NB分化，而且在体内可改善晚期NB患儿的预后。虽然一些分子参与白血病和神经元分化的维生素D3和13-顺式维甲酸之前已经被研究过，但尚未获得对所涉及的分子机制的全面理解。材料与方法：利用微阵列技术研究了2061个肿瘤发生相关RNA转录本在维生素D3和13-顺式维甲酸诱导的白血病细胞和NB细胞分化过程中的表达；SK-N-SH和CHP-134。结果：维生素D3诱导粘附分子和MHC II类分子升温。两个独立的NB细胞系暴露于13-顺式维甲酸后，43个基因下调，36个基因上调。值得注意的是，视网膜母细胞瘤（RB）家族成员RBI、p107、RB2/p130以及p300/CBP和E2F上调，而RB的抑制因子（CDK4和细胞周期蛋白A）下调。此外，酪蛋白激酶II，一种已知的促进神经生成的蛋白质，被上调。结论：这些结果表明，微阵列技术足够灵敏，可以突出NB分化的全谱分子机制，并且RB家族可能在13-顺式维甲酸诱导的NB分化中发挥核心作用。

Purpose: Leukemia and Neuroblastoma (NB) are major pediatric solid tumors with a poor prognosis. Vitamin D3 is known to induce differentiation of HL60 leukemia cell line.13-cis retinoic acid has been known not only to induce differentiation of NB in vitro, but also to improve the prognosis of children with NB in advanced stages in vivo. Although the involvement of several molecules in the leukemic and neuronal differentiation by vitamin D3 and 13-cis retinoic acid has previously been investigated, a comprehensive understanding of the molecular mechanisms involved has not been obtained. Materials and Methods: With microarray technology, we investigated the expression of 2061 oncogenesis related RNA transcripts during leukemic cell and NB cell differentiation triggered) by vitamin D3 and 13-cis retinoic acid using two NB cell lines; SK-N-SH and CHP-134. Results: Vitamin D3 induced upreguration of adhesion molecules as well as MHC class II molecules. Two separate NB cell lines demonstrated down-regulation of 43 genes and up-regulation of 36 genes after 13-cis retinoic acid exposure. Notably, retinoblastoma (RB) family members RBI, p107, and RB2/p130, as well as p300/CBP and E2F were up-regulated, whereas suppressors of RB (CDK4 and cyclin A) were down-regulated. In addition, casein kinaie II, a protein known to promote neuritogenesis, was up-regulated. Conclusions: These results suggest that the microarray technique is sensitive enough to highlight the whole spectrum of molecular mechanisms inivolved in NB differentiation, and further, the RB family may play a central role in NB differentiation induced by 13-cis retinoic acid.