The Wnt-1 proto-oncogene 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 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.
Shackleford
G M
GM
Division of Hematology-Oncology, Children's Hospital Los Angeles, California.
Willert
K
K
Wang
J
J
Varmus
H E
HE
D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019278:Matrix Metalloproteinase 3; D008565:Membrane Proteins; D008666:Metalloendopeptidases / Q000235:genetics; D008868:Microtubule Proteins; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D016716:PC12 Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D050777:Stathmin; D014157:Transcription Factors / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D050777:Stathmin; C512849:Stmn2 protein, mouse; C512848:Stmn2 protein, rat; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D014443:Tyrosine; D005346:Fibroblast Growth Factors; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3