Down modulation of N-myc, heat-shock protein 70, and nucleolin during the differentiation of human neuroblastoma cells.
Cultured human neuroblastoma (GOTO) cells were induced to differentiate by dibutyryl cyclic AMP (Bt2cAMP) and/or retinoic acid (RA). A combination of Bt2cAMP (1 mM) and RA (1 microM) yielded the most significant networks of neurites after 3 to 4 days, this being associated with the reduction of N-myc mRNA levels. Next, we examined several cellular genes that were possibly linked with changes in N-myc gene expression under these conditions. Among the genes examined, both nucleolin and a major heat-shock protein (hsp70) mRNAs showed changes concomitant with those in N-myc mRNA levels when induced by Bt2cAMP and RA. Dibutyryl cAMP alone induced several short cellular processes and caused a marked decrease in N-myc mRNA within 2 days. RA alone induced a few long and straight neurites along the longitudinal axis of individual cells and a significant decrease in growth rate but showed neither network formation nor a decrease in N-myc gene expression. These results indicate differential effects of Bt2cAMP and RA on the regulatory mechanisms of both cell proliferation and differentiation and also indicate a possible association of expression of N-myc gene with those of hsp70 and nucleolin genes.
Murakami
T
T
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Fukuoka.
Ohmori
H
H
Gotoh
S
S
Tsuda
T
T
Ohya
R
R
Akiya
S
S
Higashi
K
K
D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000097796:Nucleolin
D003994:Bucladesine; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014212:Tretinoin; D000097796:Nucleolin