Dimitroulakos J, Pienkowska M, Sun P, Farooq S, Zielenska M, Squire J A, Yeger H
Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
Int J Cancer. 1999 Jun 11;81(6):970-8. doi: 10.1002/(sici)1097-0215(19990611)81:6<970::aid-ijc21>3.0.co;2-9.
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.
我们建立了一种独特的神经母细胞瘤亲本细胞系NUB - 7，该细胞系分别经二丁酰环磷腺苷（dibutyryl cAMP）和视黄酸处理后，在体内模拟神经母细胞瘤沿神经元和雪旺细胞谱系的双潜能性。差异显示法鉴定出一个假定的新型锌指基因，作为与NUB - 7视黄酸处理相关的潜在分化反应基因。这个cDNA克隆，现命名为zf5 - 3，利用体细胞杂种将其定位到19号染色体，通过荧光原位杂交，一个更大的cDNA克隆进一步将该基因定位到13.1 - 13.2带。根据其核酸和推测的氨基酸序列确定，zf5 - 3具有4个特征性锌指DNA结合基序。zf5 - 3的表达局限于胎儿神经元、肝脏和肾脏组织及其肿瘤衍生细胞系，包括8/9的神经母细胞瘤和2/2的肾恶性横纹肌样瘤。zf5 - 3在肾脏中局限于集合小管和输尿管上皮的表达提示肾恶性横纹肌样瘤起源于外胚层。在胎儿人脑发育过程中，高水平的zf5 - 3 mRNA局限于有丝分裂活跃、未分化的神经母细胞。明显分化的形态学证据通常伴随着zf5 - 3表达的显著丧失。因此，神经元组织表达谱以及与视黄酸诱导的神经母细胞瘤成熟相关的下调表明zf5 - 3可能是其分化的潜在介导因子。
