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Mol Cell Biol, May 1998, p. 2474-2485, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Wnt-1 Induces Growth, Cytosolic beta -Catenin, and Tcf/Lef Transcriptional Activation in Rat-1 Fibroblasts

C. S. Young,1 Marina Kitamura,2 Stephen Hardy,2 and Jan Kitajewski1,*

Department of Pathology and Center for Reproductive Sciences, College of Physicians and Surgeons, Columbia University, New York, New York 10032,1 and Cell Genesys Inc., Foster City, California 944042

Received 14 October 1997/Returned for modification 4 December 1997/Accepted 2 February 1998

Genetic evidence suggests that regulation of beta -catenin and regulation of Tcf/Lef family transcription factors are downstream events of the Wnt signal transduction pathway. However, a direct link between Wnt activity and Tcf/Lef transcriptional activation has yet to be established. In this study, we show that Wnt-1 induces a growth response in a cultured mammalian cell line, Rat-1 fibroblasts. Wnt-1 induces serum-independent cellular proliferation of Rat-1 fibroblasts and changes in morphology. Rat-1 cells stably expressing Wnt-1 (Rat-1/Wnt-1) show a constitutive up-regulation of cytosolic beta -catenin, while membrane-associated beta -catenin remains unaffected. Induction of cytosolic beta -catenin in Rat-1/Wnt-1 cells is correlated with activation of a Tcf-responsive transcriptional element. We thus provide evidence that Wnt-1 induces Tcf/Lef transcriptional activation in a mammalian system. Expression of a mutant beta -catenin (beta -CatS37A) in Rat-1 cells does not result in a proliferative response or a detectable change in the cytosolic beta -catenin protein level. However, beta -CatS37A expression in Rat-1 cells results in strong Tcf/Lef transcriptional activation, comparable to that seen in Wnt-1-expressing cells. These results suggest that Wnt-1 induction of cytosolic beta -catenin may have functions in addition to Tcf/Lef transcriptional activation.

* Corresponding author. Mailing address: Department of Pathology, Columbia University, 630 West 168th St., New York, NY 10032. Phone and fax: (212) 305-3624. E-mail: jkk9{at}columbia.edu.

Mol Cell Biol, May 1998, p. 2474-2485, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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