Identification of a novel zinc finger gene, zf5-3, as a potential mediator of neuroblastoma differentiation.
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.
Dimitroulakos
J
J
Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
Pienkowska
M
M
Sun
P
P
Farooq
S
S
Zielenska
M
M
Squire
J A
JA
Yeger
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007680:Kidney Neoplasms; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D009474:Neurons; D009928:Organ Specificity; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C119501:ZF5-3 protein, human; D014212:Tretinoin; D003994:Bucladesine