1,25-dihydroxyvitamin D3 regulates the expression of N-myc, c-myc, protein kinase C, and transforming growth factor-beta2 in neuroblastoma cells.
1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) alters the proliferation of neuroblastoma cells in culture in part via a nerve growth factor (NGF)-mediated pathway. This suggests that factors other than NGF also play a role in the growth arrest induced by 1,25(OH)2D3. To more fully characterize the effect of 1,25(OH)2D3 on neuroblastoma cells, we treated the cells with 10(-8) M 1,25(OH)2D3 and examined the cells for changes in the expression of N-myc, c-myc, transforming growth factor-beta2 (TGF-beta2), and protein kinase C (PKC) activity. Our results show that 1,25(OH)2D3 causes a decrease in the expression of N-myc and c-myc, as well as a two-fold increase in total PKC activity and a dose-dependent increase in TGF-beta2 expression. These results show that 1,25(OH)2D3 regulates the expression of growth-regulatory factors other than NGF in neuroblastoma cells and that 1,25(OH)2D3 influences the growth of neural cells via multiple growth regulatory pathways.
Veenstra
T D
TD
Nephrology Research Unit, Mayo Clinic Foundation, Rochester, Minnesota 55905, USA.
Windebank
A J
AJ
Kumar
R
R
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C; D002117:Calcitriol