Wnt/beta-catenin signaling suppresses apoptosis in low serum medium and induces morphologic change in rodent fibroblasts.
Wnt/beta-catenin signaling plays important roles in tumorigenesis in certain tumors as well as during development. However, the mechanism of tumorigenesis mediated by this signaling remains to be elucidated. We investigated the response of rodent fibroblasts to activation of Wnt/beta-catenin signaling by treatment with conditioned medium containing soluble Wnt-3a protein (W3a-CM) and by expression of a constitutive active beta-catenin gene harbored by an adenovirus vector. W3a-CM induced transcriptional activation of a beta-catenin/T-cell factor (Tcf)-responsive promoter in rodent fibroblasts such as NIH3T3, Rat-1, Swiss3T3 and Balb3T3 cells. In these cells, an increase in saturation density and an inhibition of apoptosis and/or promotion of growth in low-serum medium were induced by treatment with W3a-CM. In Rat-1 cells, morphologic changes were also induced. All these alterations were reversible. Moreover, the inhibition of apoptosis of NIH3T3 cells in low-serum medium and the morphologic changes in Rat-1 cells, but not the increase in saturation density, were also induced by ectopic expression of a constitutive active beta-catenin gene. These results suggested that activation of Wnt/beta-catenin signaling induces inhibition of apoptosis and morphologic changes in these cells.
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Yoshihide
Y
Ueda
Makoto
M
Hijikata
Shinji
S
Takagi
Ritsuko
R
Takada
Shinji
S
Takada
Tsutomu
T
Chiba
Kunitada
K
Shimotohno
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D015870:Gene Expression; D015151:Immunoblotting; D008156:Luciferases / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003470:Culture Media; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin; D008156:Luciferases