Guerrero I, Pellicer A, Burstein D E
Department of Pathology, N.Y.U. Medical Center, New York 10016.
Biochem Biophys Res Commun. 1988 Feb 15;150(3):1185-92. doi: 10.1016/0006-291x(88)90754-1.
In order to develop a model system for investigating the role of ras genes in neuronal differentiation, a construct consisting of a mouse N-ras oncogene linked to a dexamethasone-inducible promoter was devised and transfected into a subline of the PC12 rat pheochromocytoma cell line. Clonal lines were isolated which extended neurite-like processes within one day of exposure to dexamethasone. N-ras had a strong antiproliferative effect on these cells. These effects were reversible after removing dexamethasone. Elevation of mRNA for ornithine decarboxylase (ODC) was detected 6-18 hours after induction of N-ras by dexamethasone. The effects of ras on cell division, differentiation and cell size were analogous, but not identical to the effects of NGF on PC12 cells. One NGF action, induction of c-fos mRNA did not occur in ras-induced cells indicating that c-fos induction is unnecessary for both neurite outgrowth and for subsequent induction of ODC mRNA. The ability of ras to induce ODC, a division promoting enzyme, may also be relevant to the transforming actions of ras oncogenes.
为了开发一个用于研究ras基因在神经元分化中作用的模型系统，设计了一种构建体，其由与地塞米松诱导型启动子相连的小鼠N-ras癌基因组成，并将其转染到PC12大鼠嗜铬细胞瘤细胞系的一个亚系中。分离出克隆系，这些克隆系在暴露于地塞米松一天内长出神经突样突起。N-ras对这些细胞具有强烈的抗增殖作用。去除地塞米松后，这些作用是可逆的。地塞米松诱导N-ras后6-18小时检测到鸟氨酸脱羧酶（ODC）的mRNA升高。ras对细胞分裂、分化和细胞大小的影响与神经生长因子（NGF）对PC12细胞的影响相似，但不完全相同。NGF的一种作用，即诱导c-fos mRNA，在ras诱导的细胞中未发生，这表明c-fos诱导对于神经突生长和随后诱导ODC mRNA均不是必需的。ras诱导ODC（一种促进分裂的酶）的能力也可能与ras癌基因的转化作用有关。
