Gene Expression Profiles of Differentiating laukemia cells.

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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.