The induction of ret by Wnt-1 in PC12 cells is atypically dependent on continual Wnt-1 expression.
Wild type PC12 pheochromocytoma cells that had been infected with a Wnt-1-carrying virus and thus express Wnt-1 (PC12/Wnt-1) are known to acquire the same flat cell phenotype as that of spontaneously occurring PC12 flat cell variants except that the latter do not presently express Wnt-1. Flat cell variants of PC12 cells exhibit markedly altered morphology and gene expression. In order to assess the possibility that the spontaneously occurring flat cell variants could have been induced in wild type PC12 cells by previous transient expression of the cell's endogenous Wnt-1, we have isolated PC12/Wnt-1 cells expressing little or no Wnt-1. In spite of absent Wnt-1 expression, they retained their flat cell morphology, glutamate/aspartate transporter activity, increased neu mRNA levels and lack of both norepinephrine transporter activity and nerve growth factor-induced differentiation. Thus, Wnt-1 expression is not required to maintain the flat cell phenotype. However, we identified one gene, ret, whose mRNA level in PC12 was not only increased by Wnt-1 expression, but whose increased mRNA level was also dependent on continual Wnt-1 expression. This finding suggests that the induction of ret by Wnt-1 can be used to elucidate the Wnt-induced signalling pathway in mammalian cells.
Zheng
S
S
Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90095, USA.
Ramachandran
B
B
Haigh
J R
JR
Palos
T P
TP
Steger
K
K
Howard
B D
BD
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000310:Adrenal Gland Neoplasms; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid; D001483:Base Sequence; D001692:Biological Transport; D002454:Cell Differentiation; D006224:Cricetinae; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism; D029721:Drosophila Proteins; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010673:Pheochromocytoma; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D001224:Aspartic Acid; D017931:DNA Primers; D004298:Dopamine; D029721:Drosophila Proteins; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C495247:WNT1 protein, human; C495245:Wnt1 protein, rat; C416649:Ret protein, Drosophila; C495001:Ret protein, rat