Ultraviolet light induces expression of p53 and p21 in human skin: Effect of sunscreen and constitutive p21 expression in skin appendages

Abstract

It has been suggested that p53 plays an important role in skin carcinogenesis. The p21 molecule acts as a downstream effector of wild-type p53 by enacting cell cycle arrest. We studied p53 and p21 expression in sun-exposed skin. Healthy volunteers were exposed to ultraviolet irradiation (UVA + UVB) in normal, previously non-sun-exposed skin, and skin biopsies were taken. Immunohistochemically detectable p53 and p21 were quantified, and the pattern of distribution was recorded. p53 was induced in epidermal cells 4 h after irradiation and returned to nearly normal levels after 120 h. Suprabasal cells showed a peak at 4 h, whereas basal cells peaked later, at 48 h. In epidermis, the expression of p21 was induced with a pattern that mirrored that of p53. In addition, p21 was induced in mesenchymal cells of the upper dermis, where there was no p53, suggesting an alternative pathway for p21 induction. Topical sunscreen and pigmentation (skin type 5) nearly eliminated UV-induced expression of p53 and p21. In contrast to the complete absence of p53 in skin never exposed to UV-radiation, p21 reactivity was found in sharply demarcated areas of anagen hair follicles and sebaceous glands, as well as in scattered epidermal cells. The prevalence and distribution suggest a physiologic role of p21 in stopping the cell cycle in terminally differentiating skin epithelium. Archival skin material from the vicinity of skin lesions with variable sun exposure were also stained for p53. There was an increased 'disperse' reactive staining pattern in skin samples excised in the summer as compared with less sunny seasons. Intensely stained p53 foci were detected as 'compact bands' in morphologically normal epidermis, predominantly in sun-exposed areas of the skin, suggesting the existence of clonal proliferation of p53 mutated keratinocytes. These data show that p53 and p21 play a role in the human skin response to UV exposure and that p21 is implicated in the homeostasis of differentiating skin appendages.