Retinoic acid inhibits phosphatidylinositol turnover only in RA-sensitive while not in RA-resistant human neuroblastoma cells.
Phosphatidylinositol (PI) turnover has recently been implicated in the regulation of cell proliferation and transformation. We have investigated its role in differentiation using LAN-1 cells, a human neuroblastoma cell line which can be induced to differentiate along the neuronal pathway by retinoic acid (RA), and a derivated RA-resistant subline of it (LAN-1-res). We have found that treatment of LAN-1 cells with RA is followed by a rapid decrease of inositol phospholipid metabolism, using myo-[1,2-3H] inositol or [1,(3)-3H] glycerol. Analysis of labelled phosphatidylinositol metabolites from prelabelled LAN-1 cells indicated a rapid decrease of inositol (1,4,5)-trisphosphate and (1,2) diacylglycerol within 1 min. of induction of differentiation by RA, while no changes were observed in RA-treated LAN-1-res cells. These findings indicate that phosphoinositides-derived metabolites may be directly implicated in the induction processes of RA-triggered NB cell differentiation.
Lanciotti
M
M
Pediatric Oncology Research Laboratory, G. Gaslini Children's Hospital, Genoa, Italy.
Longone
P
P
Cornaglia-Ferraris
P
P
Ponzoni
M
M
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D004075:Diglycerides; D010716:Phosphatidylinositols; D014212:Tretinoin