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Human neuroblastoma cell lines that express N‐ myc without gene amplification
Author(s) -
Wada Randal K.,
Seeger Robert C.,
Brodeur Garrett M.,
Einhorn Peggy A.,
Rayner Sylvia A.,
Tomayko Mary M.,
Reynolds C. Patrick
Publication year - 1993
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19931201)72:11<3346::aid-cncr2820721134>3.0.co;2-e
Subject(s) - neuroblastoma , cell culture , gene duplication , cancer research , biology , microbiology and biotechnology , gene , metastasis , n myc , cell , gene expression , genetics , cancer , ganglioneuroma
Background . About one half of aggressive neuroblastomas lack N‐ myc amplification. Cell lines from such tumors are needed to determine the biological basis of aggressive tumor behavior. Methods . Neuroblastoma cell lines were established from a primary tumor (SMS‐LHN) and a bone marrow metastasis (LA‐N‐6) of two children with Stage IV neuroblastoma. Although both cell lines and their original tumors lacked N‐ myc genomic amplification, these patients died of progressive disease. Results . SMS‐LHN and LA‐N‐6 can be distinguished from primitive neuroectodermal tumor (PNET) lines by cell surface antigen expression and catecholamine production. Cytogenetic analysis of each cell line revealed unique genetic rearrangements, whereas both lines showed abnormalities involving chromosome 2. Neither cell line contained double‐minute chromosomes, homogeneously staining regions, a 1p chromosomal deletion, or t(11;22). The growth rates of these two new lines in vitro and in vivo (as xenografts in nude mice) are slower than N‐ myc amplified neuroblastoma lines. Both lines express greater amounts of N‐ myc RNA and protein relative to nonneuroblastoma cell lines (including PNET), although not to the extent of cell lines with N‐ myc genomic amplification. Conclusions . The relatively large amount of N‐ myc expression in these two new cell lines suggests that N‐ myc expression without amplification could play a role in the pathogenesis of some neuroblastomas. These cell lines should be useful for investigating mechanisms and consequences of N‐ myc gene activation other than genomic amplification.