Expression of the ret proto-oncogene in human neuroblastoma cell lines and its increase during neuronal differentiation induced by retinoic acid.

Previously we observed specific expression of the ret proto-oncogene (proto-ret) in human neuroblastoma cell lines. A neuronal subline and non-neuronal sublines were isolated from the SK-N-SH cell line, which is composed of a heterogeneous cell population. Expression of proto-ret was detected in the neuronal subline, named SH-4305, but not in three non-neuronal sublines. Expression of proto-ret in the SH-4305 cells increased markedly after treatment with retinoic acid for 1 day, with concomitant morphological change, namely neurite outgrowth, and induction of neurofilament mRNA expression. Induction of proto-ret expression seemed to be correlated with neurite outgrowth and increase of neurofilament mRNA expression. These data suggest that the proto-ret product plays a role in neuronal differentiation.