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

✍ Scribed by Jim Dimitroulakos; Malgorzata Pienkowska; Peizhu Sun; Saqba Farooq; Maria Zielenska; Jeremy A. Squire; Herman Yeger

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 531 KB
• Volume: 81
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990611)81:6<970::aid-ijc21>3.0.co;2-9

✦ Synopsis

We established a unique parental neuroblastoma cell line, NUB-7, which mimics the bipotentiality of neuroblastoma in vivo along neuronal and Schwann cell lineages following dibutyryl cAMP and retinoic acid treatments, respectively. 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 chromosome 19 using somatic cell hybrids, and a larger cDNA clone further localized this gene to band 13.1-13.2 by fluorescent in situ hybridization. zf5-3 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 collecting tubules and ureter epithelium is suggestive of an ectodermal histogenesis of malignant rhabdoid tumors of kidney. During development of the fetal human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts. Morphological evidence of overt differentiation 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 zf5-3 as a potential mediator of their differentiation.