OVEREXPRESSION OF THE NERVE GROWTH FACTOR-INDUCIBLE PC3 IMMEDIATE-EARLY GENE IS ASSOCIATED WITH GROWTH-INHIBITION

PC3 (pheochromocytoma cell-3) is an immediate early gene isolated as s equence induced in the rat PC12 cell line during neuronal differentiat ion by nerve growth factor (NGF), PC3, which is expressed in vivo in t he neuroblast when it ceases proliferating and differentiates into a n euron, has partial homology with two antiproliferative genes, BTG1 and Tob. Here we report that overexpression of PC3 in NIH3T3 and PC12 cel ls leads to marked inhibition of cell proliferation, In stable NIH3T3 clones expressing PC3, the transition from G(1) to S phase was impaire d, whereas the retinoblastoma (RB) protein was detected as multiple is oforms of M(r) 105,000-115,000 (indicative of a hyperphosphorylated st ate) only in low-density cultures. Such findings are consistent with a condition of growth inhibition, Thus, PC3 might be a negative regulat or of cell proliferation, possibly acting as a transducer of factors i nfluencing cell growth and/or differentiation, such as NGF, by a RE-de pendent pathway. This is the first evidence of a NGF-inducible immedia te early gene displaying antiproliferative activity.