PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis.

PC3TIS21/BTG2 is member of a novel family of antiproliferative genes (BTG1, ANA/BTG3, PC3B, TOB, and TOB2) that play a role in cellular differentiation. We have previously shown that PC3TIS21/BTG2 is induced by nerve growth factor (NGF) at the onset of neuronal differentiation in the neural crest-derived PC12 cell line, and is a marker for neuronal birth. We now observe that PC3TIS21/BTG2 ectopically expressed in PC12 cells synergises with NGF, similarly to the cyclin-dependent kinase inhibitor p21, potentiating the induction of the neuronal markers tyrosine hydroxylase and neurofilament 160 kDa. Furthermore, PC3TIS21/BTG2 protects from apoptosis elicited by NGF deprivation in terminally differentiated PC12 cultures. Such effects might be a consequence of the arrest of cell cycle exerted by PC3TIS21/BTG2, or expression of a sensitizing (neurogenic) property of the molecule.