Wnt-1 induces growth, cytosolic β-catenin, and Tcf/Lef transcriptional activation in Rat-1 fibroblasts
Wnt-1 induces growth, cytosolic β-catenin, and Tcf/Lef transcriptional activation in Rat-1 fibroblasts
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DOI：
10.1128/mcb.18.5.2474
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发表时间：
1998-05-01
影响因子：
5.3
通讯作者：
Kitajewski, J
中科院分区：
文献类型：
--
作者：
Young, CS;Kitamura, M;Kitajewski, J
遗传证据表明，β-连环蛋白的调节和 Tcf/Lef 家族转录因子的调节是 Wnt 信号转导途径的下游事件。然而，Wnt 活性和 Tcf/Lef 转录激活之间的直接联系已经建立。在这项研究中，我们证明 Wnt-1 可诱导培养的哺乳动物细胞系 Rat-1 成纤维细胞的生长反应。 Wnt-1 诱导 Rat-1 成纤维细胞的血清依赖性细胞增殖和形态变化。稳定表达 Wnt-1 (Rat-1/Wnt-1) 的 Rat-1 细胞表现出胞质 β-连环蛋白的组成性上调，而膜相关的 β-连环蛋白不受影响。 Rat-1/Wnt-1 细胞中胞质 β-连环蛋白的诱导与 Tcf 响应转录元件的激活相关。因此，我们提供了 Wnt-1 在哺乳动物系统中诱导 Tcf/Lef 转录激活的证据。 Rat-1 细胞中突变型 β-连环蛋白 (β-CatS37A) 的表达不会导致增殖反应或胞质 β-连环蛋白水平的可检测变化。然而，Rat-1 细胞中的 beta-CatS37A 表达导致强烈的 Tcf/Lef 转录激活，与表达 Wnt-1 的细胞中所见的情况相当。这些结果表明，Wnt-1 诱导胞质 β-连环蛋白可能具有除 Tcf/Lef 转录激活之外的功能。
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 Set 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.