Inverse expressions of the N-myc oncogene and beta 1 integrin in human neuroblastoma: relationships to disease progression in a nude mouse model system.
A nude mouse model for human neuroblastoma has been developed to examine possible relationships between amplification/over-expression of the N-myc oncogene and altered regulation of expression of specific integrin subunits during tumor progression. Subcutaneous (ectopic) or intra-adrenal (orthotopic) injection of the neuroblastoma cell lines SK-N-SH or IMR-32 has generated a number of derivative tumor cell lines. Tumor cell lines derived from SK-N-SH cells (which do not express N-myc) or IMR-32 cells (which over-express N-myc) produce tumors at higher rates when re-injected into the subcutaneous space of nude mice. Moreover, cell lines derived from tumors initiated by IMR-32 cells exhibit shorter latent periods than do IMR-32 cells direct from tissue culture. With regard to integrin subunit expression, SK-N-SH and related cell lines express high levels of beta 1 integrin, which is associated with the alpha 2 and alpha 3 integrin subunits (predominantly alpha 3). IMR-32 cells display reduced beta 1 expression, and that which is produced is not associated with common alpha subunits. LaN1 cells, which express N-myc at even higher levels than do IMR-32 cells, express even less beta 1. Interestingly, the tumor-derived cell lines (especially those from tumors initiated in adrenal glands) also exhibit reduced integrin expression compared with the parental cell lines; this reduction is associated with the enhanced tumor take rate observed when the cells are re-injected into nude mice. Our results raise the possibility of a relationship between over-expression of N-myc and down-regulation of beta 1 integrin expression (possibly some alpha subunits also). In addition, the data suggest that human neuroblastoma-derived cell lines which exhibit reduced integrin expression display more aggressive tumor growth in nude mice.
Judware
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Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106.
Lechner
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R
Culp
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LA
D000818:Animals; D016259:Genes, myc; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
D019012:Integrin beta1; D016023:Integrins