Montagnoli A, Guardavaccaro D, Starace G, Tirone F
Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy.
Cell Growth Differ. 1996 Oct;7(10):1327-36.
PC3 (pheochromocytoma cell-3) is an immediate early gene isolated as sequence induced in the rat PC12 cell line during neuronal differentiation by nerve growth factor (NGF). PC3, which is expressed in vivo in the neuroblast when it ceases proliferating and differentiates into a neuron, has partial homology with two antiproliferative genes, BTG1 and Tob. Here we report that overexpression of PC3 in NIH3T3 and PC12 cells leads to marked inhibition of cell proliferation. In stable NIH3T3 clones expressing PC3, the transition from G1 to S phase was impaired, whereas the retinoblastoma (RB) protein was detected as multiple isoforms of M(r) 105,000-115,000 (indicative of a hyperphosphorylated state) only in low-density cultures. Such findings are consistent with a condition of growth inhibition. Thus, PC3 might be a negative regulator of cell proliferation, possibly acting as a transducer of factors influencing cell growth and/or differentiation, such as NGF, by a RB-dependent pathway. This is the first evidence of a NGF-inducible immediate early gene displaying antiproliferative activity.
PC3（嗜铬细胞瘤细胞-3）是一种即刻早期基因，它是在大鼠PC12细胞系中，经神经生长因子（NGF）诱导神经元分化过程中作为序列被分离出来的。PC3在体内神经母细胞停止增殖并分化为神经元时表达，与两个抗增殖基因BTG1和Tob具有部分同源性。在此我们报告，PC3在NIH3T3和PC12细胞中的过表达导致细胞增殖受到显著抑制。在稳定表达PC3的NIH3T3克隆中，从G1期到S期的转变受损，而视网膜母细胞瘤（RB）蛋白仅在低密度培养物中被检测为分子量105,000 - 115,000的多种异构体（表明处于高磷酸化状态）。这些发现与生长抑制状态一致。因此，PC3可能是细胞增殖的负调节因子，可能通过RB依赖途径作为影响细胞生长和/或分化的因子（如NGF）的转导分子。这是NGF诱导的具有抗增殖活性的即刻早期基因的首个证据。
