Phosphatidylinositol turnover is not a general regulator of neuroblastoma cell differentiation: comparison between two differentiating agents, retinoic acid and gamma-interferon.

ABSTRACT

The turnover of phosphatidylinositol (PI) is believed to constitute a crucial step in the signaling pathways for stimulation of cells by a variety of bioactive substances, including differentiating agents; however decisive evidence for the idea has not been obtained. In the present paper, we investigated the involvement of PI turnover in cell differentiation using a human neuroblastoma cell line, LAN-1, which can be induced to differentiate along the neuronal pathway by both retinoic acid (RA) and gamma-interferon (gamma-IFN). Analysis of labelled phosphatidylinositol metabolites from prelabelled cells indicated a rapid decrease of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol within 1 min of induction of LAN-1 cell differentiation by RA, while no changes were observed in gamma-IFN-treated cells. These findings indicate the occurrence of decreased inositol phospholipid turnover in RA-treated LAN-1 cells and suggest that phosphoinositide-derived metabolites may not constitute general regulators of cellular differentiation.