The Wnt/β-catenin Signaling Pathway in Melanocyte and Melanoma Development

被引:0
|
作者
Delmas, V. [1 ]
Champeval, D. [1 ]
Fuciani, F. [1 ]
Herbette, A. [1 ]
Kumasaka, M. [1 ]
Alberti, C. [1 ]
Demirkan, N. [1 ]
Larue, L. [1 ]
机构
[1] CNRS Inst Curie, UMR 146, F-91405 Orsay, France
关键词
Wnt; immortalisation; tumour suppressor; p16INK4a;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In several cancers, including melanoma, Mutations in beta-catenin lead to its stabilization and translocation from the plasma membrane to the nucleus where it regulates transcription. Although nuclear beta-catenin clearly contributes to malignant transformation, little is known about how it exerts its effects. To investigate the function of beta-catenin in melanoma, we generated transgenic mice in which a stabilized, nuclear form of beta-catenin was targeted specifically to the melanocyte lineage. Although we observed no melanomas in these transgenic mice, primary skin melanocytes derived from these animals immortalized very efficiently through beta-catenin-mediated silencing of the p16(Ink4A) promoter. These findings provide a direct molecular link between P-catenin and the melanoma susceptibility gene p16(INK4a), and reveal a novel pathway for inactivation of p16(INK4a) expression and senescence bypass relevant to it wide range of cancers.
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页码:63 / 68
页数:6
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