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Increased epidermal functioning wild-type p53 expression in vitiligo.

Karin U Schallreuter¹, Stefanie Behrens-Williams, Tahira P Khaliq

¹Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK. K.Schallreuter@bradford.ac.uk

Experimental Dermatology

|June 26, 2003

Summary

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Patients with vitiligo exhibit elevated levels of functioning wild-type p53, a key tumor suppressor. This finding may explain the surprisingly low incidence of skin cancer in vitiligo patients despite reduced melanin protection.

Area of Science:

Dermatology
Oncology
Molecular Biology

Background:

Vitiligo patients have less melanin and higher oxidative stress, yet lower skin cancer risk.
Previous studies indicated p53 overexpression in vitiligo, but its functionality was uncharacterized.

Purpose of the Study:

To investigate the functionality of elevated p53 in vitiligo epidermis.
To explore the expression of p53 and related proteins (MDM-2, PCNA, p21) and thioredoxin reductase (TR) in vitiligo skin.

Main Methods:

Functional color yeast assay (FASAY) to assess p53 functionality.
Protein and mRNA expression analysis of p53, MDM-2, PCNA, p21, and TR in vitiligo and control skin.
Evaluation of narrowband UVB treatment effects on p53 expression.

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Main Results:

Demonstrated overexpression of functional wild-type p53 in both depigmented and pigmented vitiligo epidermis.
Found unchanged expression of MDM-2, PCNA, and p21.
Observed decreased thioredoxin reductase (TR) protein levels, but unaffected mRNA, correlating with p53 activity.

Conclusions:

This is the first evidence of persistently elevated, functional wild-type p53 in human epidermis.
Hypothesize that up-regulated functional p53 contributes to the reduced risk of actinic damage and skin cancer in vitiligo patients.