Shackleford G M, Willert K, Wang J, Varmus H E
Division of Hematology-Oncology, Children's Hospital Los Angeles, California.
Neuron. 1993 Nov;11(5):865-75. doi: 10.1016/0896-6273(93)90116-9.
The product of the Wnt-1 proto-oncogene is a secreted glycoprotein that is normally produced in regions of the embryonic neural tube. We show here that expression of mouse Wnt-1 cDNA in the rat PC12 pheochromocytoma cell line causes a dramatic conversion from a round to a flat cell morphology. In addition, PC12 cells expressing Wnt-1 (PC12/Wnt-1) fail to extend neurites after treatment with NGF, despite the presence and activation of high affinity NGF receptors encoded by the trk gene and the induction of early response genes. Furthermore, PC12/Wnt-1 cells fail to express several neuron- and chromaffin-specific genes, indicating that PC12/Wnt-1 cells have assumed a new phenotype. Although NGF and FGF utilize similar signal transduction pathways in PC12 cells, only FGF is capable of inducing a morphological response and synthesis of transin mRNA in PC12/Wnt-1 cells.
原癌基因Wnt-1的产物是一种分泌型糖蛋白，通常在胚胎神经管区域产生。我们在此表明，在大鼠嗜铬细胞瘤PC12细胞系中表达小鼠Wnt-1 cDNA会导致细胞形态从圆形急剧转变为扁平形。此外，尽管存在由trk基因编码的高亲和力神经生长因子（NGF）受体并被激活，且早期反应基因也被诱导，但用NGF处理后，表达Wnt-1的PC12细胞（PC12/Wnt-1）无法长出神经突。此外，PC12/Wnt-1细胞无法表达几种神经元和嗜铬细胞特异性基因，这表明PC12/Wnt-1细胞呈现出一种新的表型。尽管NGF和FGF在PC12细胞中利用相似的信号转导途径，但只有FGF能够在PC12/Wnt-1细胞中诱导形态学反应和反式激活蛋白mRNA的合成。
