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Increased epidermal functioning wild‐type p53 expression in vitiligo
Author(s) -
Schallreuter Karin U.,
BehrensWilliams Stefanie,
Khaliq Tahira P.,
Picksley Steven M.,
Peters Eva M. J.,
Marles Lee K.,
Westerhof Wiete,
Miehe Bärbel,
Fanghänel Jochen
Publication year - 2003
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2003.00084.x
Subject(s) - vitiligo , epidermis (zoology) , cancer research , wild type , skin cancer , melanocyte , biology , melanoma , medicine , cancer , dermatology , mutant , gene , genetics , anatomy
Abstract: Despite the lack of protective melanin and increased oxidative stress due to mM concentrations of epidermal H 2 O 2 in vitiligo, there is no significantly increased risk for chronic actinic damage and non‐melanoma skin cancer. Therefore the question arises, which protective mechanisms could be involved in the skin of these patients preventing the initiation of these cancers. Recently an overexpression of p53 has been shown in vitiligo. Unfortunately there was no further characterization of this elevated p53. Employing a functional colour yeast assay, the study presented herein demonstrates for the first time the overexpression of a functioning wild‐type p53 protein in both depigmented and ‘normal’ pigmented epidermis of patients with vitiligo compared with healthy controls. Surprisingly long‐term narrowband UVB (311 nm) treatment does not alter this expression. Moreover, MDM‐2, PCNA and p21 protein expression remain unchanged compared with healthy controls. This increased epidermal p53 in vitiligo coincides with decreased thioredoxin reductase (TR) protein levels in both depigmented and pigmented skin whereas mRNA expression is unaffected. Because TR is one transcriptional target of p53, these results support a wild‐type functionality, which was further supported by the specific p53 FASAY yeast test. To our knowledge this is the first example of persistent elevated functioning wild‐type p53 in humans. Based on our results we hypothesize that the low incidence for actinic damage, basal cell and squamous cell carcinoma as documented in vitiligo could well reside in a protective function of up‐regulated wild‐type p53.