Calcyclin gene expression was evaluated in different neuroblastoma cell lines and during neuronal differentiation induced by retinoic acid. Calcyclin gene expression was more frequently detected in epithelial-type or Schwann-like cells rather than in neuroblastic cells. This result indicates an increase of G1 cell fraction, which may explain the limited growth potential usually observed for these cells. LAN-5 cell (neuronal type) differentiation experiments showed that calcyclin gene is detectable after 4 days of retinoic acid treatment, which induces G1 phase accumulation (as detected by cytofluorometric analysis), and cell growth arrest. Otherwise, neither block of cell proliferation by 0.5% fetal calf serum medium nor addition of 15% fresh fetal calf serum after cell arrest induce calcyclin expression. The increase of calcyclin mRNA levels during cell differentiation shows that calcyclin gene expression is associated with neuronal differentiation. This bivalent role of the calcyclin gene, which is normally expressed in the G1 phase of the cell cycle but also expressed during retinoic acid-induced neuroblastoma cell differentiation, suggests that (at least in neuroblastoma cells) the gene is subject to a complex transcriptional regulation.
The work was supported by Associazione Italiana per lo Ricerca sul Cancro, Milan, and by G. Gaslini Grant 871 70F.3.