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Wnt/β-catenin signaling suppresses apoptosis in low serum medium and induces morphologic change in rodent fibroblasts

✍ Scribed by Yoshihide Ueda; Makoto Hijikata; Shinji Takagi; Ritsuko Takada; Shinji Takada; Tsutomu Chiba; Kunitada Shimotohno


Publisher
John Wiley and Sons
Year
2002
Tongue
French
Weight
474 KB
Volume
99
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

Wnt/β‐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/β‐catenin signaling by treatment with conditioned medium containing soluble Wnt‐3a protein (W3a‐CM) and by expression of a constitutive active β‐catenin gene harbored by an adenovirus vector. W3a‐CM induced transcriptional activation of a β‐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 β‐catenin gene. These results suggested that activation of Wnt/β‐catenin signaling induces inhibition of apoptosis and morphologic changes in these cells. © 2002 Wiley‐Liss, Inc.