Diverse responses to retinoid in morphological differentiation, tumorigenesis and N-myc expression in human neuroblastoma sublines.
We established the subline RT-BMV-C6 from the parent human neuroblastoma cell line RT-BM by a process that required repeated subculture of cells, which were prone to disaggregation. RT-BMV-C6 and the parent cloned line, RT-BM-1, had an identical marker chromosome, confirming that both lines were derived from a common progenitor. In the analysis of surface antigen expression, RT-BMV-C6 did not react with UJ-127-11, Leu7 or KP-NAC2 MAbs to which RT-BM-1 showed positive binding. The levels of both N-myc amplification and expression in RT-BMV-C6 were twice as high as the level obtained in RT-BM-1. Colony-forming efficiency in soft agar was 2.0 +/- 0.8% for RT-BMV-C6 and 3 times greater than that for RT-BM-1 (0.6 +/- 0.1%). When 100 x 10(6) cells of RT-BM-1 and RT-BMV-C6 were inoculated into nude mice, tumor incidence was significantly higher for RT-BMV-C6 (6/6; 100%) than for RT-BM-1 (0/6; 0%). Our data show that N-myc is closely related to tumorigenicity in NB. When RT-BM-1 and RT-BMV-C6 were co-cultured with a new synthetic retinoid, polyprenoic acid (E5166), and dibutyryl cyclic AMP, RT-BM-1 was induced to neuronal differentiation, defined by the formation of neuronal processes and expression of neurofilaments, whereas RT-BMV-C6 was not. However, when exposed to E5166, N-myc expression of RT-BMV-C6 was more strongly reduced than that of RT-BM-1, and colony formation of RT-BMV-C6 was significantly inhibited as compared to RT-BM-1. These findings suggest that the reduction of N-myc expression might closely correlate with growth inhibition accompanying neuronal differentiation of neuroblastoma cells.
Hino
T
T
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Sugimoto
T
T
Matsumura
T
T
Horii
Y
Y
Inazawa
J
J
Sawada
T
T
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D009857:Oncogenes; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D014212:Tretinoin; D003994:Bucladesine; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid