Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line

• Published in: Cancer research (Chicago, Ill.) Vol. 51; no. 23; pp. 6338 - 6345
• Main Authors: FOLEY, J, COHN, S. L, SALWEN, H. R, CHAGNOVICH, D, COWAN, J, MASON, K. L, PARYSEK, L. M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.1991
• Subjects: Biological and medical sciences; Cell Differentiation - drug effects; Gene Expression Regulation, Neoplastic - genetics; Genes, myc - genetics; Humans; Intermediate Filaments - chemistry; Karyotyping; Medical sciences; Nerve Growth Factors; Neural Crest - enzymology; Neuroblastoma - chemistry; Neuroblastoma - genetics; Neuroblastoma - pathology; Neurology; Phenotype; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Tretinoin; Tumor Cells, Cultured - chemistry; Tumor Cells, Cultured - pathology; Tumors of the nervous system. Phacomatoses; Vimentin - analysis; Human; Interconversion; Nervous system diseases; Exploration; Neuroblastoma; Malignant tumor; Gene expression; Cell subpopulation; Northern blotting; Phenotype; Messenger RNA; Tumor progression; Onc gene; Immunofluorescence; Southern blotting; Sympathic nervous system
• ISSN: 0008-5472; 1538-7445

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.