Identification of a novel zinc finger gene, zf5-3, as a potential mediatorof neuroblastoma differentiation

We established a unique parental neuroblastoma cell line, NUB-7, which mimi cs the bipotentiality of neuroblastoma in vivo along neuronal and Schwann c ell lineages following dibutyryl cAMP and retinoic acid treatments, respect ively. Differential display identified a putative novel zinc finger gene as a potential differentiation-responsive gene coincident with retinoic acid treatment of NUB-7. This cDNA clone, now designated zf5-3, was mapped to ch romosome 19 using somatic cell hybrids, and a larger cDNA clone further loc alized this gene to band 13.1-13.2 by fluorescent in site hybridization. zf 5-3 possesses 4 characteristic zinc finger DNA-binding motifs as determined by its nucleic acid and proposed amino acid sequence. Expression of zf5-3 is restricted to fetal neuronal, hepatic and renal tissues and their tumor- derived cell lines, including 8/9 neuroblastomas and 2/2 malignant rhabdoid tumors of kidney. The restricted expression in the kidney of zf5-3 to coll ecting tubules and ureter epithelium is suggestive of an ectodermal histoge nesis of malignant rhabdoid tumors of kidney, During development of the fet al human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts, Morphological evidence of overt diff erentiation was generally accompanied by a marked loss in zf5-3 expression. Therefore, the neuronal tissue expression profile and the down-regulation coincident with retinoic acid-induced neuroblastoma maturation implicate zf 5-3 as a potential mediator of their differentiation. (C) 1999 Wiley-Liss, Inc.