Multi-hormonal regulation of IGFBP-6 expression in human neuroblastoma cells.

Abstract

Previous work has shown that neuroblastoma cells secrete IGFBP-2, -4 and -6 and that expression of these proteins is regulated by retinoic acid (at-RA) which promotes differentiation in these cells. Other agents also induce differentiation of neuroblastoma cells: these include the 9- cis and 13- cis isomers of at-RA, 1,25 dihydroxy- vitamin D3 (VD3), triidothyronine (T3) and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Nine- cis and 13- cis isomers of at-RA increased IGFBP-6 expression, but decreased IGFBP-2 and IGFBP-4. VD3 stimulated IGFBP-6 and IGFBP-2 expression, whereas T3 inhibited IGFBP-6 expression without affecting IGFBP-2. TPA markedly enhanced expression of all three IGFBPs produced by SK-N-SH cells. Since IGFBP-6 secretion is associated with the arrest of proliferation in neuroblastoma cells and is regulated by the combined actions of differentiation factors, we subcloned the proximal promoter of human IGFBP-6 (nt -766/+1) into a pCAT expression vector so as to examine modulation of its transcriptional activity. VD3 and TPA were capable of stimulating promoter activity, T3 depressed it and at-RA and its 9- cis and 13- cis isomers had no effect. These results confirm the high sensitivity of IGFBP-6 expression to these differentiation agents, essentially at transcriptional level.

• Authors: D Chambery, B De Galle, E Ehrenborg, S Babajko
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 10 Issue 6 Pg. 349-59 (Dec 2000) ISSN: 1096-6374 [Print] Scotland
• PMID: 11161966 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Carcinogens
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 4
• Insulin-Like Growth Factor Binding Protein 6
• Triiodothyronine
• Cholecalciferol
• Tretinoin
• RNA
• Luciferases
• Chloramphenicol O-Acetyltransferase
• Tetradecanoylphorbol Acetate

Topics

• Antineoplastic Agents (pharmacology)
• Base Sequence
• Blotting, Northern
• Blotting, Western
• Carcinogens
• Cell Division
• Chloramphenicol O-Acetyltransferase (metabolism)
• Cholecalciferol (pharmacology)
• Cloning, Molecular
• Down-Regulation
• Humans
• Insulin-Like Growth Factor Binding Protein 2 (biosynthesis)
• Insulin-Like Growth Factor Binding Protein 4 (biosynthesis)
• Insulin-Like Growth Factor Binding Protein 6 (biosynthesis, genetics)
• Isomerism
• Luciferases (metabolism)
• Models, Genetic
• Molecular Sequence Data
• Neuroblastoma (metabolism)
• Plasmids (metabolism)
• Promoter Regions, Genetic
• RNA (metabolism)
• Sequence Analysis, DNA
• Tetradecanoylphorbol Acetate
• Transcription, Genetic (drug effects)
• Tretinoin (pharmacology)
• Triiodothyronine (pharmacology)
• Tumor Cells, Cultured
• Up-Regulation