The Vitamin D Receptor Is a Wnt Effector that Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis

被引：103

作者：

Palmer, Hector G. ^{[1
]}

Anjos-Afonso, Fernando ^{[2
]}

Carmeliet, Geert ^{[3
]}

Takeda, Hikaru ^{[4
]}

Watt, Fiona M. ^{[1
]}

机构：

[1] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England

[2] Canc Res UK London Res Inst, London, England

[3] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Leuven, Belgium

[4] Yamagata Univ, Sch Med, Dept Dermatol, Yamagata, Japan

来源：

PLOS ONE | 2008年 / 3卷 / 01期

关键词：

D O I：

10.1371/journal.pone.0001483

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We have investigated how Wnt and vitamin D receptor signals regulate epidermal differentiation. Many epidermal genes induced by beta-catenin, including the stem cell marker keratin 15, contain vitamin D response elements (VDREs) and several are induced independently of TCF/Lef. The VDR is required for beta-catenin induced hair follicle formation in adult epidermis, and the vitamin D analog EB1089 synergises with beta-catenin to stimulate hair differentiation. Human trichofolliculomas (hair follicle tumours) are characterized by high nuclear beta-catenin and VDR, whereas infiltrative basal cell carcinomas (BCCs) have high beta-catenin and low VDR levels. In mice, EB1089 prevents beta-catenin induced trichofolliculomas, while in the absence of VDR beta-catenin induces tumours resembling BCCs. We conclude that VDR is a TCF/Lef-independent transcriptional effector of the Wnt pathway and that vitamin D analogues have therapeutic potential in tumors with inappropriate activation of Wnt signalling.

引用

页数：11

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