THE WNT-1 PROTOONCOGENE INDUCES CHANGES IN MORPHOLOGY, GENE-EXPRESSION, AND GROWTH-FACTOR RESPONSIVENESS IN PC12 CELLS

The product of the Wnt-1 proto-oncogene is a secreted glycoprotein tha t is normally produced in regions of the embryonic neural tube. We sho w here that expression of mouse Wnt-1 cDNA in the rat PC12 pheochromoc ytoma cell line causes a dramatic conversion from a round to a flat ce ll morphology. In addition, PC12 cells expressing Wnt-1 (PC12/Wnt-1) f ail 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 cel ls fail to express several neuron- and chromaffin-specific genes, indi cating that PC12/Wnt-1 cells have assumed a new phenotype. Although NG F 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.