Multi-hormonal regulation of IGFBP-6 expression in human neuroblastoma cells.
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.
Chambery
D
D
Institut National de la Santé et de la Recherche Médicale, Unité de Recherches sur la Croissance, Différenciation et Processus tumoraux, Hôpital Saint Antoine, Paris, 75571, France.
De Galle
B
B
Ehrenborg
E
E
Babajko
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens; D002455:Cell Division; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology; D003001:Cloning, Molecular; D015536:Down-Regulation; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000096:biosynthesis* / Q000235:genetics; D007536:Isomerism; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D002273:Carcinogens; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D014284:Triiodothyronine; D002762:Cholecalciferol; D014212:Tretinoin; D012313:RNA; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate