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

共 34 条

[31] Vitamin D3 analogs stimulate hair growth in nude mice [J].

Vegesna, V ;

O'Kelly, J ;

Uskokovic, M ;

Said, J ;

Lemp, N ;

Saitoh, T ;

Ikezoe, T ;

Binderup, L ;

Koeffler, HP .

ENDOCRINOLOGY, 2002, 143 (11) :4389-4396

[32] Epidermal stem cells: an update [J].

Watt, Fiona M. ;

Lo Celso, Cristina ;

Silva-Vargas, Violeta .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2006, 16 (05) :518-524

[33] Wnt proteins are lipid-modified and can act as stem cell growth factors [J].

Willert, K ;

Brown, JD ;

Danenberg, E ;

Duncan, AW ;

Weissman, IL ;

Reya, T ;

Yates, JR ;

Nusse, R .

NATURE, 2003, 423 (6938) :448-452

[34] Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning [J].

Yoshizawa, T ;

Handa, Y ;

Uematsu, Y ;

Takeda, S ;

Sekine, K ;

Yoshihara, Y ;

Kawakami, T ;

Arioka, K ;

Sato, H ;

Uchiyama, Y ;

Masushige, S ;

Fukamizu, A ;

Matsumoto, T ;

Kato, S .

NATURE GENETICS, 1997, 16 (04) :391-396

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