Beta-catenin/Tcf activation partially mimics the transforming activity of Wnt-1 in Rat-1 fibroblasts.
We have previously demonstrated that Wnt-1 induction of cytosolic beta-catenin and Tcf/Lef transcriptional activation correlate with enhanced proliferation, survival, and post-confluent growth in Rat-1 fibroblasts. To examine whether beta-catenin mediates the biological responses to Wnt-1 in this context, we characterized Rat-1 clonal cell lines expressing different levels of a mutant, stabilized beta-catenin (beta-cateninS37A). Clonal lines exhibit elevated cytosolic and nuclear beta-cateninS37A and Tcf transcriptional activation, comparable to that elicited by Wnt-1 expression. However, expression of beta-cateninS37A does not promote growth of Rat-1 cells in serum-free conditions and only partially promotes growth post-confluence, when compared to that induced by Wnt-1 expression. As ectopic expression of beta-cateninS37A only partially mimics Wnt-1 effects on Rat-1 cells, we conclude that Wnt-1 signaling elicits biochemical events that act in addition to beta-catenin/Tcf signaling to promote cell growth.
Young
C S
CS
Department of Pathology and OB/GYN, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Masckauchan
T N H
TN
Kitajewski
Jan
J
D019943:Amino Acid Substitution; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002472:Cell Transformation, Viral; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D008156:Luciferases / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D016297:Mutagenesis, Site-Directed; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D051176:beta Catenin; D008156:Luciferases